Unit 4: The nervous system

Drugs used to treat cancer include:

chemotherapy drugs can include alkylating agents: In this case, these agents when a cell is exposed to them; prevent DNA replication. Mitotic inhibitors are drugs which work by preventing formation or shortening of the mitotic spindle. The problems with these drugs is that they prevent division of all cells that are actively going through the cell cycle, not just can cancer cells. (They cannot target just cancer cells these drugs essentially prevent any cell that is actively trying to go through the cell cycle to create more daughter cells.) The fact that you prevent healthy cells from dividing indiscriminately along with cancer cells, causes many of chemotherapy side effects. (Cisplatin Is a chemotherapy drug classified as an alkylating agent. Which phase of the cell cycle would a cell exposed to this be able to complete? G1 interphase) (Which type of cell would you expect to be most affected by chemotherapy drugs? The answer should be the number that has the lowest amount of days. (Cell lining the stomach: 2 to 9 days) The cell that would be most affected is the cell that is most rapidly going through cell division (The cells that are being killed off and replicate/reproduced more frequently)

Active transport

moving things against a concentration gradient. (moving things (for example, sodium ions) from where they are low to where they are even higher. The same with potassium (for example) we can move it against a concentration gradient; so, instead of having to rely on diffusion (moving from high to low) we could move molecules from where they are low, to where they are already high. Requires energy (come in the form of ATP)

At rest, a neuron should have:

negative charge inside compared to outside More potassium ions (K+) inside compared to outside More sodium ions (Na+) outside compared to inside

DNA to Proteins recap

DNA is contained and 23 pairs of homologous chromosomes. (46 total, One in each pair from our parent cells) DNA - gene - amino acids - protein Proteins dictate all of the functions of a cell (We have about 20,000 genes in total, which means our cells makes at-least 20,000 different proteins.) Ex: hemoglobin gene that codes the hemoglobin protein. And the p53 gene that codes for the p53 protein.

excitatory neurotransmitter

Excitation: Occurs if the neurotransmitter causes sodium channels to open. sodium channels for facilitated diffusion would allow sodium ions to rush in, then sodium enters the receiving cell (if that's what this neurotransmitter is doing) and the inside becomes more positive. Excitatory neurotransmitter: when one neuron releases this type of neurotransmitter the receiving cell responds by becoming more positive which means we are more likely to have an action potential. (And then a new action potential begins in the receiving cell.)

Recent studies found exercise increases myelination of neurons by neuroglia. What effect would more myelin have on neurons?

Faster communication within and between neurons

Inhibitory neurotransmitter

Inhibition: Occurs if the neurotransmitter causes potassium channels to open. (All neurons have the sodium potassium pump) Potassium leaves the receiving cell, the inside becomes more negative and prevents an action potential in the receiving cell. (So now instead of communication being that one neuron causes the next neuron to have an action potential, sometimes the communication involves one neuron preventing the next neuron from having an action potential; it's inhibitory because it releases and inhibitory neurotransmitter.)

Tetrodotoxin is a toxin found in certain parts of a pufferfish. The toxin is responsible for many fatalities every year when it is accidentally ingested when the fish is eaten. Tetrodotoxin prevents the opening of sodium (Na+) channels responsible for facilitated diffusion in all neurons of the central nervous system. Why would this toxin be lethal?

It prevents neurons from being able to generate an action potential and It prevents neurons from being able to generate an action potential

Mutations in the cell cycle checkpoints (continued)

So, if tumor suppressor proteins and Proto-onco proteins don't function properly, then the cell can lose control of the cell cycle and division. (instead of having this orderly regulated progression: where we stop at the G1 checkpoint (check to make sure DNA is ok) copy it, check to make sure that's it's been copied correctly, go through mitosis to make sure they've been lined up correctly and then finally create our two new cells. (This is supposed to be our quarterly mechanism for proceeding in cell division.) And that is controlled by tumor suppressor genes & proto-oncogenes (and the proteins that they encode) Proteins essentially act like our breaks & our accelerator; Tumor suppressor genes stop when the cells not supposed to be progressing, and our proto-oncogenes make proteins that allows the cell to go when it is supposed to be proceeding through the cell cycle.

During an action potential the cell depolarizes due to:

Sodium ions (Na+) entering the cell by facilitated diffusion

Ions

Sodium ions (Na+) one positive net charge. Potassium ions (K+) one positive net charge. Both will give away one electron and form a positively charged ion. (since they are positively charged, wherever they move in a cell (either in or out ) it's going to be taking that positive charge with it.

What do antianxiety medications like benzodiazepines and alcohol have in common?

Their presence prevents action potentials

Neurotransmitters effects

There are hundreds of different neurotransmitters (these chemicals that neurons release at the synaptic cleft) and each neuron generally releases only one. (Example, Dopamine serotonin, adrenaline ' glutamine, endorphins, acetylcholine) Depending on the type of neurotransmitter, the receiving neuron can respond in a couple of different ways. The receiving neuron can be excited (Likely to fire an action potential) or inhibited (less likely or Unlikely to fire an action potential)m Many neurotransmitters receptors are ion channels, triggered to open when a neurotransmitter binds. (Facilitates diffusion)

Cancer

broadly defined as abnormal cells that are dividing without control. The normal orderly manner that we use to ensure cells are dividing only when they're supposed to divide is lost. (Which can result in the development of cancer)

cancer characteristics (formation of tumors)

- Another characteristic of cancer cells is that they tend to form these masses known as tumors. This results from contact inhibition - A process in normal cells when they're touching one another; they prevent each other from further division. (This would be an environmental cue that inhibits cell division) So normally if you imagined normal cells growing in a Petri dish, they would grow as a single layer of cells. In a normal cell, if you damage or remove some of them, the cells nearby that site of damage would enter the cell cycle and divide. (The proteins encoded for by proto-oncogenes would stimulate neighboring cells to progress through the cell cycle and divide.) So normally proto-oncogenes would stimulate that to occur, once we have replaced those damaged cells; cell division will stop, and contacting inhibition will inform the cell that they were in contact with there neighbor, so it shouldn't be going through the cell cycle anymore. But in a cancer cell, they lack this process of contact inhibition. They start to grow on top of one another. so in this case neighboring cells will enter the cell cycle and start to divide but they no longer have this contact inhibition that once they have restored the single layer of cells they would stop cell division. So, Instead cancer cells don't receive that cue to stop division and keeps dividing. So division is going to continue even after that single layer is restored (the cells continue to go through the cell cycle and create more cells and more cells and this leads to tumor formation.) Another characteristic of cancer cells is that the tend to form masses (tumors) because they dont exhibit contact inhibition)

cancer characteristics (infinite cell divisions)

- Another is that they have unlimited rounds of the cell cycle in infinite cell divisions. (Telomeres: these repetitive DNA sequences on the end of our chromosomes; don't code for proteins but are important for regulating DNA replication) One of the mutations that cancer cells accumulate during carcinogenesis is that they are able to express the telomerase gene. (This is a gene which most cells have, but they don't make. So, we have the recipe for this in most of our cells, but most of our cells do not follow that recipe and they don't make this protein. In the case of cancer cells, they accumulate mutations that allow them to turn on the expression of this gene and to start making telomerase protein. (Telomerase protein rebuilds the telomeres so that they don't shorten. So instead of getting shorter after each replication (until ultimately the cell reaches senescence), telomerase rebuilds that to your mirror so that it goes back to being full length. So what that means is that these cells never enter the senescence. (So cancer cells acquire this ability to make telomerase protein and therefore they can divide indefinitely.) They don't enter senescence because they never lose their telomere, they can go through an infinite number of cell division because DNA replication (which happens in S phase and requires that telomere) can continue since these cells constantly rebuild the telomere and never enters senescence.

Mitosis (Prophase)

- Prophase (first phase of mitosis) where our chromosomes are going to be condensing down further. (Then the nuclear membrane breaks down to free the chromosomes) (During prophase the nucleus breaks down. The membrane surrounding all of the genetic information breaks down and frees the chromosomes; so now they are released and they can move around the cytoplasm.) - Are going to have special protein fibers called mitotic spindle that are going to form and attach to the centromere's of sister chromatids. And these are what's going to allow us to move these around the cell. (To divide them in an organized fashion, The mitotic spindle will attach to the centromere To help us move those sister chromatids around; and to divide them up.)

Cocaine

A powerful stimulant. It alters signaling from synapsis that use the neurotransmitter dopamine. (Dopamine used by neurons in the reward circuit) How it functions is that it blocks the active transport proteins that removes dopamine from the synapse. (Cocaine is blocking this active transport protein, what that means is now our dopamine transporter gets blocked; Now dopamine is going to hang out in the synapse longer, which means if it stays there longer, It stays bound to its receptor longer and the signaling to the receiving neuron increases.) So, whatever that person is doing is perceived as highly rewarding and euphoric. (So the brain is perceiving this as rewarding and it's telling you to repeat this behavior even though it's an illicit drug.)

Causes of cancer (acquired)

Acquired mutations happen as a result of exposure to environmental mutagens. (mutagens are defined as agents that cause DNA mutations) And the list of things that are considered mutagens is constantly growing and changing as we learn about more things that can cause DNA mutations) Some that we have known about for a while or carcinogens. (chemicals that are mutagens) good examples of these would be asbestos which is highly associated with lung cancer (this is often found in old homes so alot of the insulation in old homes) Benzopyrene is a component of cigarette smoke (also an example of a carcinogen) a chemical that when you inhale it it makes it more likely for your DNA to experience a mutation. In inherited mutations, you might not inherit any mutations in your p53 gene but an exposure to a carcinogen could cause a mutation in one or both of them. (Or you might inherit one good gene and one bad gene and exposure to a carcinogen throughout your lifetime may end up causing the mutation in the one good copy that you have. Other mutagens include things like radiation. So, UV light (sunlight is a great example) X-rays and nuclear radiation All damage DNA and cause mutations. And then lastly, HPV (viruses) can cause mutations. In addition to HPV which are known to infect cells and interfere with the function of tumor suppressor and or proto-oncogenes, so that were no longer able to properly regulate the cell cycle.

Action potential continued

Action potential's are self propagating; that means each action potential generates another along the entire length of the axon So, when we first start an action potential closest to the cell body, those sodium channels coming in (causing depolarization) are going to cause adjacent/nearby sodium channels to open as well. What determines how fast it goes (speed of propagation) depends on whether or not that axon is myelinated. In an unmyelinated axon, action potential stimulate adjacent/nearby parts of the axon membrane to produce an action potential. (for example: The sodium channels that initiate the depolarization phase , has to be really close to one another; so they are all able to stimulate one another down the entire length of the axon.) Unmyelinated axons are usually covering short distances ( For example, interneurons within the spinal cord - they don't have to transmit a signal very far so they don't necessarily have to be myelinated) Because of that movement is really slow (it's about 1 m/s) because every single section of the axon has to initiate this brief reversal in its charge. A myelinated axon, the action potential only occurs at the nodes of ranvier; jumping from one to the next. (Instead of needing to be communicated to the space right next to it, the signal can jump over the space) This essentially acts like insulation; it skips/hops over that region that's myelinated completely. (This happens really fast about 100 m/s.) So the action potential does not need to occur along every section of the axon. Myelinated axons you'll see in regions that have further to communicate, so within regions of the brain (for example) or a motor neuron. (so in a motor neuron the axons can be 2 to 3 feet long) if it's a motor neuron for example this may be running down to control the muscles of your foot or your toes) thats a really long distance to transmit that information - and in that case, if you used an unmyelinated axon it could take a long time to initiate a response. (But because we have myelinated axons it happens really rapidly.) What would happen if you prevented the opening of sodium channels responsible for facilitated diffusion in the sensory neurons? Sensory neurons will not have an action potential.

Neurotransmitters removal

After this receiving neuron responds, we have to prevent continuous stimulation of the receiving cell. (We want to send that signal, but once it's been received we want to shut it off.) In order to do that, we have to remove neurotransmitters from the synapse. To get rid of them now, (Once the cellular response is initiated) We have to get rid of that neurotransmitter; there's generally a couple of ways that neurons do this: — One, Degradation: degradation essentially means that we have an enzyme that is in the synaptic cleft that breaks down the neurotransmitter. (For example, and this is what happens when motor neurons communicate with muscle; There is an enzyme that is always in the synaptic cleft, after the neurotransmitter (called acetylcholine) is released, the enzyme is there and will break it down.) The enzyme helps to inactivate the neurotransmitter, so that it can no longer bind to a receptor, and no longer initiate the cellular response. (This is useful because then we are ready for another signal to come. It will give the cell a chance to respond, and if we need to respond again- another action potential will arrive, another round of exocytosis will occur, the neurotransmitter can bind again and create a new cellular response.) — The other option is reuptake: Reuptake is active transport proteins that pump the neurotransmitter back into the sending cell to be repackaged and reused. (Sometimes broken down often times recycled, and it's put back into a vesicle that's ready for release again) This will be a reuptake protein that uses active transport to move that neurotransmitter out of the synaptic cleft. Latrotoxin, Found in black widow spider venom, induces massive exocytosis of neurotransmitters from neurons in the absence of an action potential. How might this anti-venom work? Blocking neurotransmitters receptors on muscle cells, can't initiate an effect if you block its receptors (We won't get a cellular response)

Alcohol

Alcohol also acts on inhibitory neurotransmitter's in different regions usually more widespread. so this increase The opening of most inhibitory neurotransmitters receptors scattered throughout the central nervous system. So alcohol is going to be increasing the effect of this inhibitory neurotransmitter effect on a receiving cell. (so this will prevent action potential's in many regions of the brain) so this gives a general sensation of depression; so this is a central nervous system depressant meaning that it slows down signaling in all regions of the brain.) There's also a high risk of overdosing (depressed neurons that control breathing and heart rate) Because we are essentially decreasing signaling to tell our lungs to inhale and exhale, which decreased the cardiovascular system to circulate blood; so there's an overdose risk associated with this because it depresses most of the central nervous system and most of the synapses within the central nervous system.

Neuron structure (axon)

An axon is a single long extension (from the cell body) that carries a signal in the form of a nerve impulse, towards another neuron or a target tissue. (For example, Interneurons might be communicating with a motor neuron, Motor neurons might be communicating with a muscle etc.) So the axon is what's going to convey that information (So, if the dendrites sense or get activated) that information is going to be sent down the axon and transmitted towards a target tissue or another neuron via its long extension. Bundles of axons from multiple neurons form nerves. (so if we take the same neuron and imagine it out in the peripheral nervous system; a nerve would actually represent many axons of different neurons bundled together).

P53

An example of a tumor suppressor gene that encodes a protein that controls the G1 checkpoint. P53 is a tumor suppressor gene that work here at the G1 checkpoint, This protein that is made by the P 53 gene monitors for DNA damage and mutations. (This is important because we want to make sure that there is no DNA damage, mutations, or errors being passed down to the two daughter cells.) If there is DNA damage or a mutation, P53 protein will go to that site on the DNA and recruit repair proteins to fix it. (P 53 hits the brakes, stop cell division and triggers these proteins to come over and fix that damage) Once it is repaired, then the cell is allowed to proceed through the rest of the cell cycle. (Goes through S phase, G2, mitosis, Cytokinesis where it makes two new daughter cells.) If the damage is too severe, P 53 will initiate cell death (Apoptosis) (Ex: sunburn) P53 is critically important because at least half of all human cancers have mutations in this P53 gene.

External control of the cell cycle

Another way that we can control the cell cycle, is through external control. (The cues outside of a cell. (not necessarily outside of the body.) so within the body, you can receive cues like hormones, chemical signals and growth factors that either stimulate a cell to divide or inhibit a cell from dividing. And in response to those external cues, this cell can respond by turning on some of its proteins (So we can have activation of gene expression) And that cell can start making proteins, (By first making RNA, having it go to the ribosomes, the ribosomes produce a protein ... and that protein that's made in response, can regulate progression through the cell cycle. So the cell can respond to environmental cues by either going through the cell cycle more rapidly or stopping progression through the cell cycle. One of the ways that it does so is by using proteins that code for these checkpoints. So there's many different proteins that can be made within a cell, both in response to those environmental cues, (And sometimes just constantly produced not necessarily just in response to a cue) And these proteins regulate and control progression of a cell through the cell cycle. (Like a traffic light) These are all encoded for by the DNA (genes make proteins) Two of these different classes of genes control the cell cycle, proto-oncogenes are a group of genes that code for proteins which promote the cell cycle and prevent apoptosis. (In this case proto-oncogenes would encourage a cell to proceed through the phases of the cell cycle, and produce more cells while preventing apoptosis.) (Green light) Tumor suppressor genes: function in the opposite way. These are a group of genes (set of instructions) that code for proteins, which inhibit the cell cycle and promote apoptosis. So, when these proteins are around, they stop the cell from progressing through the cell cycle, And they encourage the cell to go through programmed cell death if necessary. (Red light)

Regulating the Cell Cycle

Apoptosis: Throughout life, cell division is balanced by the process of apoptosis, or programmed cell death. (Apoptosis is an intentional removal of excess cells that are not needed) This occurs when cells are no longer needed or have become excessively damaged. (Ex: sunburn and fingers fused together.)

BRCA 1 and BRCA 2

BRCA 1 and two Our tumor suppressor genes, they assist at the G1 checkpoint. They encode DNA repair proteins in several types of cells. Encode proteins that are going to inhibit progression through the cell cycle at G1 checkpoint And they essentially are what the P53 protein calls over to repair the DNA. (So that hopefully the cell can get repaired and can progress on through the rest of the cell cycle.) Prevent cells from entering S phase with damage DNA, Because hopefully BRCA 1 and 2 can do thief job and repair that damage. One of the kinds of cells that these functions in are in breast cells. ( mAssociated with breast cancer because when they don't function properly we lack these repair proteins often times in individuals with breast cancer; Which means P53 isn't working, BRCA 1 and or 2 aren't working, and as a result we don't have a means to stop cells with the damage, we don't have a means to repair the DNA damage and we end up creating cells and allowing them to proceed through the cell cycle when they have DNA damage and that can lead to the development of cancer.

Local anesthetics

Block the sensation of pain by removing sodium channels and sensory neurons from opening. So if we look at this overall process of what is happening, what this is acting on is those sodium channels that are responsible for starting the action potential. ( ex: if Novocain is around and a stimulus is applied, that sodium channel can't open - sodium can't diffuse in; which means we don't have depolarization. So what happens in response to that stimulus being applied, is nothing. There is no action potential (if our sensory neuron isn't generating an action potential what that means is it's not sending that signal down to the next neuron in line. (Ex: interneuron, which would help us perceive pain.) So the neurons is not sending information down its axon; so it can't communicate with the next cell in line. In the presence of a local anesthetic, there is no signal that there is a painful stimulus (it's still there, you just don't feel anything.)

opiates

Can be licit and elicit, some are prescribed and can be legal but can also be abused because they act on pain perception circuits Example would be heroin and morphine and their derivatives. And the pain perception circuits that they act on utilize two substances/chemicals. The first is substance P, which is a neurotransmitter used to signal pain in the central nervous system. When substance P is released it binds to receptors (postsynaptic cell membrane) and they signal the presence of pain. (increases our pain signaling and pain perception) We have a natural system that helps to modulate and decrease our pain response, and that is known as our endorphins. Endorphins are released by nearby neurons and bind to receptors on the axon terminal; so rather than binding to the Postsynaptic receptors, they actually have receptors here on the axon terminal, and when endorphins bind they actually block the release of substance P. So when endorphins are around m, essentially you are helping to alter your pain signaling. increased endorphins means less substance p, less substance P means less pain perception. Opiates are essentially taking advantage of this natural endorphins system. So opiates alter pain signaling, Because they mimic endorphins and binds to their receptor. So when opiates like heroin or morphine are present, they bind to the same receptors that endorphins would naturally bind to, they block the release of substance P and they block pain signaling. So when we block the release of substance P we get a decrease in pain sensation. What do amphetamines and opiates have in common; they both mimic naturally occurring neurotransmitters.

Causes of cancer

Cancer can result from mutations in genes which code for proteins that regulate the cell cycle checkpoints. (Such as tumor suppressor genes and proto-oncogenes) If we have a mutation in these what is ends up happening is that instead of making proteins that inhibit the cell cycle, instead of making proteins that stimulate the cell cycle when they are supposed to; we end up with these defective proteins that don't function properly. (Defective tumor suppressor protein and defective proto-oncogene protein)

Central Nervous System (CNS)

Central nervous system two components function in slightly different ways. The spinal cord can provide a means of communication between the brain and the peripheral nervous system. For example if we voluntarily decided we wanted to move our arm, that command is initiated in the brain and it reaches the muscle that we want to move by going first through the spinal cord and then out to the peripheral nervous system. The central nervous system is also responsible for processing information and making a decision about the commands that it wants to initiate. For example, touching. It is processing the information about what it is you're touching, whether you want to be touching it, and if you should or want to move your hand away from what you are touching. The central nervous system can make all of those decisions for us.

Neurons

Communication is a crucial function of neurons. (So, the sensory neuron needs to be able to communicate that there is a hot and painful burner (stimulus) out here. The Interneuron needs to communicate that information to the brain (so we know if there) and to the motor neurons, so we can initiate a response. Our motor neuron needs to be able to communicate with our muscles to tell it to contract.) Neurons are going to communicate with nerve impulses. Nerve impulses are electrochemical changes, used to convey information along the length of a neurons axon and to its neighboring neurons. (Electrochemical means that there are two components to these nerve impulses. There are electrical components (so, in this case neurons are going to use electrical changes to transmit a signal down the length of the axon using electrical changes.) (action potential) Once we get to the point where we need to communicate with the next neuron in line or with our target cell (our effector) We are no longer going to use electrical communication, At the end to communicate with the next neuron in line, we are going to use chemical signaling. (neurotransmitters) electrical signaling is down the length of the axon; chemical signaling is now when that electrical signal reaches the end of the axon; neuron's are going to use a chemical signal to communicate with the next cell. (At the end of the axon we are going to have the structures (axon terminals) And those are going to use exocytosis, to release chemicals that are then going to bind to the target cell and it's receptors to initiate a response there. so neurons will use electrochemical signaling to send a signal down the length of their axon and then his send that signal to the next neuron in line.

Neuron structure (dendrites)

Dendrites are responsible for receiving signals from the environment (so for example, putting your hand on a hot burner - that signal was received from the environment) or from other neurons. One neuron communicates with another - they can communicate by having another neuron connects to the dendrites of this neuron; this is where it would receive that information for example if it was an interneuron it would receive information from a sensory neuron here at its dendrites. And it does so by using receptors. Receptors are proteins that are embedded in the cell membrane, whose job is to bind and respond to environmental stimuli to initiate a response in this neuron. (For example, heat, cold, pressure, chemicals, Neurotransmitters releases from other neurons, or from tissue injury - pain, etc.) With the example of heat, putting our hand on a hot burner; what activates this protein receptor is a change in temperature. So, this protein receptor might get activated when it's exposed to heat and in response to that, we activate this neuron and then signal that information. (Other receptors can respond to changes in temperature in the opposite direction. Instead of responding to heat, they are activated in the presence of cold. Others detect pressure and etc.) Dendrites are primarily where you will find a high number of these receptors that allow neurons to respond to those very different stimuli.

Structure of DNA when we go through the process of cell division

During cell division, DNA is wound tightly around proteins that are called histones and condensed into chromosomes. ( The DNA is wound around that histone proteins to help keep it organized and compact) (Like thread on a spool. The thread would be our DNA, the spool would be a histone protein.) Human cells have 46 chromosomes that are arranged in 23 pairs. The pairs are called homologous chromosomes. (Homologous chromosomes within these pairs come from your parents, so the reason why they are organized in pairs is because we get one from our mom and one from our dad; So half of the genetic information came from my mom and the other half came for my dad) Homologous chromosomes contain genes coding for the same type of proteins but the instructions may vary. (For example thinking of our DNA as a cookbook, and our genes as recipes for a protein; as you can imagine, you have a gene (a recipe) to make a cake. you can make different kinds of cake chocolate, vanilla, red velvet etc. So, for the cakes the actual instructions might vary Because there are different kinds of cake. If we apply the same theory to are homologous pairs, you can imagine that some of your physical characteristics are dictated by these proteins that you have. (So in chromosome pair number 4 for example, the instructions that you got from your mom perhaps code for a pigment that gives your hair a brown color. On the other chromosome that came from your dad, You still got instructions for the same type of proteins to give pigment to your hair color but now the instructions might vary a little bit, maybe you got instructions for blonde hair. And the same is true for all of the genes on all of these chromosome pairs.) Homologous chromosomes come from different sources (so one came from your mom & one came from your dad) the information that they contain is not identical.

Mitosis (in detail)

During mitosis, this is where we have division of the genetic material. (DNA) (Actually divvying up DNA, making sure that each of our new cells that we are creating has its own exact copy of the DNA that are parent cells started out with. So during mitosis once we are done with the cell cycle we need to make sure that each new daughter cell created has 23 homologous chromosome pairs that are identical to the daughter. (we need to make sure that after the cell cycle is done, each daughter cell has DNA that is identical to the parents cells. 1. DNA replication (s phase) 2. Now we have our sister chromatids that are identical. 3. During mitosis we are going to be splitting up each sister chromatid and sending half to one cell and the other half to the other cell. (Mom and dad) 4.After mitosis (DNA division and Cytokinesis) were going to have new daughter cells that each have that same homologous chromosome pair as the parents. (So our parent cell it's going to be dividing to create two daughter cells that are identical to it.) Mitosis happens in 4 stages. The phases of mitosis is essentially; This is just an orderly way of lining up our sister chromatids at the center of the cell, and then breaking up our sister chromatids; so that one chromosome from each sister chromatid goes to opposite sides of the cell. (To ensure each new cell receives one of each of them.)

amphetamines and methamphetamines

First of the illicit drugs that actually replace or mimic a neurotransmitter. amphetamines and methamphetamines are structurally similar to the neurotransmitter dopamine. (So what happens is when amphetamines or methamphetamines are around they are mimicking dopamine by binding to an activating it's receptors. So anywhere where dopamine can bind, both of these drugs can also bind.) So in this case this is going to increase communication in circuits of the brain that normally use dopamine to signal for rewards and mood. (So once again your brain is going to get wired to reinforce seeking out this drug because they are activating that same pathway dopamine normally would be activating) And it thinks that this drug is signaling a good reward. The other problems with methamphetamines and amphetamines In addition to mimicking dopamine and bonding the same receptors, Is that they are not removed as effectively by the dopamine transport proteins. (This Reuptake proteins that normally remove dopamine from the synapse to end it's signaling, does not very effectively remove methamphetamine. so what that means is this drug is going to stay in the synapse longer so it's going to have two effects: Extreme euphoria "reward" and mood elevation AND it's longer lasting than typical dopamine signal. (Pseudoephedrine is similar to dopamine and methamphetamine and amphetamine.)

Control of the cell cycle: telomeres

For a cell to reproduce successfully the cell must be controlled, this includes: Controlling how many times an individual cell can go through the cell cycle (so how many times if we start with one parent cell can it divide and create more cells.) (We control this by telomeres on our DNA.) The important point of this mechanism of control is : Telomeres that control how many times a cell can divide and checkpoints which controls movements of the cell through the cell cycle are important because if they fail, this can result in unrestricted growth and cancer. (so either cells that can divide too many times(telomeres)or cells that can move through these phases to rapidly without any mechanism to stop them. (Checkpoint) Telomeres are repetitive sequences of DNA, that don't code for proteins; so, unlike the other parts of our DNA which contain genes, Telomeres are essentially protective structures at the end of our chromosomes that don't actually code for anything. When we replicate our DNA during S phase, a portion of the telomeres is lost each time the DNA is replicated. And that's simply because of the machinery that replicates the DNA; it sits on top of a portion of that telomere, And it can't copy that portion that is sitting on top of. The important result is that each time the DNA in a chromosome is replicated, a little bit of it telomeres is lost. (so it's telomere gets shorter and shorter with each round of DNA replication; Each time it passes through S phase it loses a little bit of its telomere) Once that telomere is completely gone, the DNA can not be replicated; so, the machinery to copy the DNA during S phase, can't copy the DNA, once there is no more telomere because there is nowhere for it to sit, and actually complete the replication process. Once the telomere is gone the cell enters senescence. That cell can no longer go through the cell cycle. (This means that the telomere has nothing left, That DNA and chromosome can't be copied, it's not going to be able to go through the cell cycle anymore. Now our protective cap is gone, this is essentially a way to give a finite end to that cells ability to go through the cell cycle (because if it can no longer go through the cell cycle, it enter senescence and can't copy its DNA and it's not going to divide anymore. This ensures each cell can only divide only about 50 times; Before the telomere is completely gone and that cell enters senescence. Telomerase Is a gene that rebuilds the telomere after DNA replication. what does it mean for the sperm producing cells that they make and can utilize telomerase enzyme? They are likely to divide more than 50 times. (If you are able to rebuild your telomeres, this means that your telomeres will never shorten and enter senescence)

proto-oncogenes

Function in a variety of ways to promote cell division and progression through the cell cycle. Most of these are made in response to environmental cues that signal the need for growth. Example if you cut yourself and you have damage to your skin, environmental cues would stimulate the remaining epithelial cells in the outer layer of your skin to divide. So in this case, we would have environmental cues that bind to receptors on the cell and stimulate the production of these proteins from proto-oncogenes that stimulate the cell cycle. In response to that environmental cue, this proto-oncogene makes its protein and that proteins stimulate the cell cycle. so now this cell responds by continuing through the cell cycle, copying its DNA, going through mitosis, going through cytokinesis and producing more cells as a result of these proto-oncogenes stimulating it to do so.

Three cell cycle checkpoints

G1 checkpoint: Proteins are going to assess if our DNA is damaged. (Because remember as we leave G1, we're going to enter S phase. And S phase we're going to replicate all that DNA, so before we replicate it, this G1 phase is going to be monitored by proteins that are essentially assessing the DNA for damage. (If there is DNA damage it can be repaired, if it's irreparable then the cell would go through apoptosis.) If there's either no damage to its DNA, Or the damage is repairable it'll get fixed and the cell will be committed to divide and continue into S phase when the appropriate growth signals are present and nutrients are available. G2 checkpoint: monitored by proteins that decide if the cell should continue or if it should stop. This G2 checkpoint is this chance to check for DNA replication. (Cell will proceed if DNA has properly been replicated (will be allowed to go into mitosis) Apoptosis will occur if the DNA is damaged and cannot be repaired. M checkpoint: (Happens between metaphase and anaphase) this gives us a chance to make sure we have lined up all of our sister chromatids along the equator of the cell. we want them lined up because now we're going to split them (in anaphase) and send them to opposite sides of the cell. So this gives us one last chance to make sure that everything is how we want it to be, before we create our two new cells. (Our mitosis checkpoint will only proceed through there if sister chromatids are properly aligned along the equator of the cell) (If that is passed, then the cell continues mitosis and go through cytokinesis and creates these two new cells. Each of these checkpoints are monitored by proteins that can stop (Tumor suppressor genes) and proteins that can encourage and promote movement to the next phase and ultimately cell division. (proto-oncogenes)

Example (Processes put together)

Hot burner example - Sensory neuron stimulates (Has receptors in a cell membrane that are activated by heat.) - Sensory neuron fires an action potential (high temperature activates that receptor, and that's what's going to stimulate the action potential.) (Sodium channels open depolarization happens, potassium channels open repolarization happens, and this happens on the entire length of the axon.) - Sensory neuron releases neurotransmitters (When it reaches the axon terminal now the sensory neuron is going to release neurotransmitters.) The neurotransmitter is going to bind to its receptor. - Excitatory (interneuron is stimulated) (letting sodium in) - Interneuron fires an action potential (We have an action potential going down the length of our interneuron.) - Interneuron releases an neurotransmitter (Gets released into the synaptic cleft) - Excitatory(motor neuron is stimulated) Sodium moves by facilitated diffusion) - Motor neuron fires an action potential - Motor neuron releases neurotransmitters ( muscle contracts) A toxin prevents the exocytosis of neurotransmitters from motor neurons. which of the following will be true when this toxin is present? A motor neuron will not be able to cause muscle contraction. ( Ex:Botox)

Mutations in the cell cycle checkpoints

If some of those mutations occur in the cell cycle checkpoints, then the proteins that help to regulate those cell cycle checkpoints can't carry out their functions. So, we can imagine a mutation in a gene that codes for a protein that regulates the cell cycle, if it experiences a mutation where we are producing a very different protein, (for example, our tumor suppressor genes, and proto-oncogenes) if those proteins can no longer carry out their functions, this is going to have a big impact on the cells ability to control the cell cycle. In tumor suppressor genes, If that protein can no longer carry out its job then that means we are no longer able to promote apoptosis(cell death) and no longer able to stop progression through the cell cycle. (So now the damage cells can move ' throughout the cell cycle) If we have a tumor suppressor gene that coded for a tumor suppressor protein, (Remember those were like red lights or the brakes on a car, so tumor suppressor genes stops cell division, promotes apoptosis if the cell isn't normal, so we're not creating more cells through cell division.) If we have a mutation in that tumor suppressor gene that is not a silent mutation, when we make these tumor suppressor proteins were using different amino acids and making very different proteins that can no longer carry out their function. (So instead of being able to inhibit/stop cell division, We are producing a protein that cannot function properly, so it's like our breaks and our red light is not working.) Proto-oncogenes promote cell division. (They encourage the cell to go through cell division & to divide and create more cells.) A mutation in a proto-oncogene means that these Proto-oncogene proteins that normally promote cell division when a cell is suppose to be dividing, can no longer carry out their function. So now what ends up happening is that the cell is receiving abnormal control over whether or not it's supposed to be dividing. Either its brakes aren't working properly (Tumor suppressor genes) or the greenlight to go (Proto-oncogenes) is being received when it's not supposed to be received. (These cells are abnormally progressing through the cell cycle because they have a mutation in one or both of these genes that control the cell cycle.)

p53 mutation

If there is a mutation in the P53 tumor suppressor gene, which changes the function of this protein (so not a silent mutation) and now there's DNA damage/mutation the P53 protein can't carry out its job (abnormal) and is very different from the original P53 protein. So, in this case we are no longer able to hit the brakes and our mechanism to stop is not working. So the P53 protein will fail to stop cell division and to repair that DNA, and the cell instead copy that damaged DNA and divides. (Now we are creating more cells to continue through the cell cycle that has this DNA damage/mutation because P53 protein is not there to monitor and check for that damage and to hit the brakes and stop it.) So overtime those damage cells (each of them came from this original cell that had a abnormal P53 Gene) They will also have the abnormal P53 gene and make they abnormal p53 protein; where they cannot stop cell division. This can result in the development of cancer. (Cells are now accumulating mutations, Because P 53 isn't there to catch them, stop that cell from dividing and trigger apoptosis.) (since they can't be repaired) Viral proteins interfere with the function of the P53 protein. (Produced from the human papilloma virus) Binds to and inhibit the function of P53. (So we can still end up with a development of cancer. In fact, HPVs are the leading cause of cervical cancer because they interfere with P53 protein and it's not able to do its job and when we have DNA mutations (in the DNA of a cervical cell) that P53 protein can't detect them, can't recruit repair proteins and fix it and the cells end of dividing and can create cancer cells.)

Causes of cancer (inherited)

Inherited essentially means that a mutation is passed down from one or both of your parents. Homologous chromosomes, these pairs of chromosomes that we have 23 in total (46) And the important thing about them was that we got one from each of our parents. But there are thousands of proteins encoded for on these homologous chromosomes. (P53 gene is on Homologous chromosome pair 17) And we get one P53 gene from our father and one P53 jeans for our mother. If one of them happen to have a mutation in the gene that codes for a defective P53 protein, that means that you can inherit that defective gene. (You can inherit one mutation or both mutations) If you inherit one mutation, well that means you still have one gene that still works. If you inherit both mutations (one from each parent) You have now inherited two defective P53 genes that make two defective P53 proteins. (That can lead to the development of cancer) Even if you had one Homologous chromosomes with a mutation and the other one that was fine, There is also the possibility that you can have an acquired mutation in the other P53 Gene.

Action potential

Instead of a resting potential, this is now going to be an action potential. A brief reversal in the electrical charge of the membrane along a neurons axon. So this is the process that we are going to use to send this information from the dendrites, down the axon, and towards the next cell in line. So, the action potential relies on two different protein channels in the membrane that specifically allows for facilitated diffusion of sodium ions or potassium ions. — We're going to see transport channels now in the neurons axon membrane that allow either sodium channels outside of the cell or potassium channels inside the cell. (Each will have a specific pore that only allows that ion to pass/diffuse through) These channels are closed at rest; When the pore opens, they are going to allow either sodium in or potassium (diffuse across the membrane) remember, diffusion meant that ions will move from where they have a high concentration to where they have a low concentration. (In facilitated diffusion, sodium would defuse into the cell, potassium would diffuse out of the cell) What should happen to the charge inside the cell when the channels open allowing sodium ions then potassium ions to diffuse ? When sodium diffuses the inside becomes positive (Depolarization) when potassium diffuses the inside becomes negative. (Repolarization) So now in an action potential, sodium channels on an axon are going to be stimulated to open. As a result, sodium enters the cell by diffusion, shortly after, the sodium channels open - potassium channels are stimulated to open and when it does potassium is going to go rushing out leaving the cell by the diffusion. (So sodium enters, and potassium leaves) 1. At rest (-70) our sodium potassium pump is using energy, creating concentration gradients for us (we were more negative inside than outside and we had high sodium outside, and high potassium inside) 2. A stimulus/ receptor is going to cause the sodium channels to open, enter and go through depolarization (the region where those sodium channels open are going to become positive.) 3. But then potassium channels are going to open, in this case, potassium is going to leave the cell and make the inside more negative so we are going to repolarize and go back to being negative. 4. After the action potential is done, our sodium potassium pump is going to restore our ion concentrations for us - so it's going to move that potassium back inside and that sodium back outside and we return back to our resting potential. (So sodium will be back outside the cell, while potassium will be put back into the cell)

Interphase

Interphase (The largest phase of the cell cycle) During interphase the cell is caring out it's normal functions (So, for example if it's a muscle cell is going to be carrying out the function of movement. And if it's a neuron it is carrying out communication etc.) And it is preparing for division incase it has to make new cells. Divided into three distinct parts: In G1 phase: this is where cells will grow & carry out their normal functions. (depending on what that cell job is in the body, this is where that sell is carrying out that job.) S phase: If a cell needs to divide, the first stop in preparing for cell division is going to happen in the S phase. (S phase is DNA replication, so all of the DNA is copied (so we have an exact copy of our genetic information) Produced during S phase. G2 phase: This is where the cell prepares to undergo cell division, and produces the enzymes necessary for that cell division to take place. Some cells of the body, like neurons in the central nervous system, can never divide to create more cells. Therefore, you would not expect to find neurons in the S phase or G2 phase. (G0 phase: Cell are outside in the replicative cell cycle and will never divide... essentially were cells go if they will never go through the rest of the cell cycle; so for example neurons, once we produce neurons they exist in G0 phase within the central nervous system. What that means is if they are ever damaged or destroyed other neurons cannot enter and create or replace them. so, neurons are one example of a cell that stays in G0 phase.)

Cancer is a multi step process

It doesn't result from just a single mutation because we have so many mechanisms in place to control the cell cycle; cancer actually results from an accumulation of mutations overtime. So if we think about the normal cell cycle (before we start talking about development of cancer) we have a balance of tumor suppressor genes and proto-oncogenes. Tumor suppressor proteins are hitting the brakes proto-oncogenes are hitting the gas and we have a balance where we can stimulate cell division when we are supposed to with proto-oncogenes and stop cell division when we need to so we are able to roll progression through the cell cycle in only create more cells when we need to and when it's appropriate. What can happen on a path to developing cancer is that we start to accumulate mutations. An example of a mutation being in a proto-oncogene. So, in this case instead of having a normal proto-oncogene that promotes cell division we created an oncogene. (Oncogenes are hitting the gas harder but the brakes still work.) In this case, we still have breaks that are working. So, even though our oncogenes are telling our cells to divide, progress through the cell cycle, create more cells because they are functioning abnormally; as long as our tumors suppressors genes are working we still have at least a mechanism to stop cell division. (So, we still have tumor suppressor proteins to hit the brakes and stop the cell from progressing and dividing. But, If we're unlucky and we accumulate more mutations a second mutation can occur & the tumor suppressor protein don't work. (So now we are hitting the gas really hard and we have no means to hit the brakes to stop cell division.) Now the combined effect of that first and second mutation is that we are stimulating cell division without a mechanism to inhibit it. (We are hitting the gas harder and we have no breaks.) We have abnormal cells that are progressing rapidly through the cell cycle and producing huge numbers of abnormal cells this is when we start to have cancer develop as a result of this multi step process.

diffusion

Molecules will move from where they have a high concentration to where they have a lower concentration. Most molecules don't like to move across the cell membrane by diffusion because most of them are polar or charged (so, for example, an ion can't simply move by the diffusion, even if there's a concentration gradient because it can't cross the phospholipid bilayer that forms our cell membrane.) So any polar or charged molecules can't move across the cell membrane by diffusion. An example of molecules that can cross the cell membrane using simple diffusion is oxygen and carbon dioxide (they are small, nonpolar molecules (no charge) They can freely move and diffuse from wherever they have the highest concentration to where they have the lowest concentration. (In or out of cells)

Synapsis integration

Most neurons have synapses with multiple neurons: they receive input from the axon terminal's of many neurons. essentially all of the excitatory and inhibitory signals from different neurons are summed up and decide what's going to happen in this post synaptic receiving cell.

Facilitated diffusion

Movement of molecules across cell membranes through transport protein channels. (From high concentration to low concentration) Diffusion requiring a protein carrier. (Using a transport protein and diffusion gradients) diffusion drives it, the protein carrier is the means to assist it. Example: glucose using the concentration gradient that molecules want to use from high to low; but since they are outside and can't move through the phospholipid bilayer... where going to use a transport protein that has the channel opening to let them through. The protein carrier is "facilitating" the process of diffusion. *Transporters are not always present in the membrane, the number can change in response to environmental cues. (Meaning under some conditions, there aren't any transport carriers in which those molecules wouldn't be able to enter the cell. In other conditions, these transport conditions will be added to the cell membrane and therefore allow these molecules to move by facilitated transport and facilitated diffusion. Example: glucose transporter.

Demyelination

Multiple sclerosis is an example of a progressive auto immune disease where the body attacks and destroys neuralgia that forms myelin in the central nervous system. So in this case, this causes demyelination of the central nervous system axons. (So, Neurons that we're supposed to have myelin to help with their communication, ultimately function as if they have no myelin. Because the cells of our immune system, specifically our adaptive immune system are targeting inadvertently these neuroglia cells that produce the myelin and they ultimately get destroyed. So the neuron itself is communicating as if it had no myelin wrapped around its axon when it has a demyelinating disease like multiple sclerosis. (Demyelination of a neuron in the central nervous system will have slow communication within and between neurons; Because that is myelin's primary function. (With demyelination you can still receive information, but it will be very very slowly.)

Tumor suppressor gene mutations

Normally, our tumor suppressor proteins inhibit/stop progression through the cell cycle. So when something is wrong (it's not supposed to be dividing) tumor suppressor proteins hit the brakes and don't let damage DNA progress past G1, G2 the Mitosis phase, or cytokinesis and doesn't let it produce the 2 new daughter cells. But if we have a mutation in a tumor suppressor protein we lose that ability to inhibit the cell cycle. So, in this case we might be receiving a cue externally - telling the cell not to divide, or the cell might have something going on inside the cell where it is trying to stimulate apoptosis, but because we have a mutation in this tumor suppressor gene the protein that it makes can't carry out its job anymore. (It can't hit the brakes, it can't tell the cell to stop dividing, and it can't stimulate cell death) But if we experience a mutation in the DNA that encodes a tumor suppressor protein, now we have a protein that is made that can't stop and inhibit the cell cycle. (Results in the conditions where you can't inhibit cell division; you can't stop the cell from progressing through the cell cycle.) Both mutations (in tumor suppressor proteins in proto-oncogenes) are detrimental to the cell.

Chemical

Now when you reach the end of an axon, electrical signal can't reach the next cell in line because neurons do not physically touch their connecting cells. So there's actually going to be a gap between this neuron that is trying to send information and the next cell in line that's receiving that information; the chemical part of the signaling is going to come when we reach the end of an axon. Now we are going to use these vesicles that are filled with chemicals known as neurotransmitters; that are going to help us traverse physical space between this neuron that is sending information and the cell that is receiving the information.

Mitosis: (Metaphase and anaphase)

Once our spindle has attached to our sister chromatids via there centromere, We are going to line up each sister chromatid at the center of the cell; At the cells equator. So, what we are doing is lining up the sister chromatids (Identical copies) at the center of the cell with the assistance of this mitotic spindle; so it grows and moves those sister chromatids to the center of the cell. Then what we are going to do is have the mitotic spindle break down and start to pull and shorten ; Separating our sister chromatids. Anaphase: So the mitotic spindle starts to shorten and as it does so, it pulls our sister chromatids apart at the centromere's; moving them toward opposite side of the cell. So what we've just done is those exact same copies of DNA, we are splitting it in half now. (Half of it is going to one side of the cell and the other one is going to the other side of the cell; As a result of our mitotic spindle shortening.

Mitosis (telophase and cytokinesis)

Once they have arrived at opposite sides of the cell; we are in telophase. So our chromosomes arrived at opposite sides of the cell (we successfully separated our sister chromatids, sent half to one side of the cell and the other half to the other side of the cell) and then we are going to reform our nuclear membrane around our 23 pairs of homologous chromosomes; And the cell begins to constrict at the center to get ready for actual division of the cell. So, then cytokinesis occurs; this allows us to pinch the cell in half to form two completely separate daughter cells. (So, our daughter cells now have the same complementary chromosomes as our parents cells.) (We have 46 chromosomes in total, 23 pairs In each new daughter cell that we have created.) Paclitaxel is a naturally occurring chemical made by parts of the pacific yew tree. This chemical prevents the shortening of the mitotic spindle. When cells are exposed to this chemical they cannot complete the cell cycle because.. they will not make it pass anaphase of mitosis. (Taxol Is the first successful chemotherapy drug; if this is applied to cells that are dividing rapidly, Those cells will essentially haunt in anaphase and they can't finish their division to create their two new daughter cells.)

Neurons require huge amounts of energy, in the form of ATP, resulting in the brain using more energy than any other organ in your body. Which of the following processes utilizes energy, in the form of ATP, by the neurons?

Operating the sodium-potassium pump during the resting potential

Ouabain is a plant derived toxin, used as an arrow poison in hunting and warfare. Ouabain interferes with function of the nervous system by changing a neuron's resting potential from -70 millivolts, to zero. What might this toxin be doing?

Preventing sodium-potassium pumps from working

Nervous system

Primary job is communicate: The nervous system is responsible for receiving and processing sensory information both from the external and internal environment. Does this using two major divisions: The central nervous system (CNS) which consists of the brain and the spinal cord. The peripheral nervous system (PNS) which consists of nerves which lie outside of the central nervous system.

Tumor suppressor genes

Proteins encoded for by tumor suppressor genes function in a variety of ways to inhibit cell division, stop progression through the cell cycle, or cause apoptosis (Cell death) Some of these are made in response to environmental cues that signal the need to stop growth. So in this case, there would be environmental cues that inhibit cell growth. So, these will bind to the receptors that would affect these tumor suppressor genes from being made into proteins that inhibit the cell cycle. (So that environmental cue is now turning on these tumor suppressor genes, so we go to our recipe and make tumor suppressor proteins that inhibit the cell cycle & promote apoptosis if they need to. Most of these proteins though are always around and they're constantly working to stop unnecessary division. (the default state) BPA Is in industrial chemical that has been used to make certain plastic since the 1960s. However, recent studies suggested BPA to interfere with the function of tumor suppressor proteins. What problem because could this cause in cells? In the presence of BPA cells will not be able to inhibit cell division and stop the progression through the cell cycle. (This is problematic because this will interfere with the cells ability to stop cell division when its not suppose to be happening. (Abnormal)

Peripheral Nervous System (PNS)

Responsible for bringing information to the central nervous system (for example, sensation - when you were touching something) Peripheral nervous system will bring that information to the central nervous system (the spinal cord and brain) so that information can be processed and it's also responsible for bringing commands from the central nervous system back out. For example, if you wanted to move your arm that information would come from the central nervous system and be conveyed out through the peripheral nervous system. So the peripheral nervous system has essentially two way communication with the central nervous system.

S phase (more detailed)

S phase: If a cell needs to divide, the first stop in preparing for cell division is going to happen in the S phase. (S phase is DNA replication, so all of the DNA is copied (so we have an exact copy of our genetic information) Produced during S phase. Cells that are going to create new cells will enter into a replicated phase (s phase) What happens is during S phase of interphase, if we have DNA replication (we copy all of the DNA contained in this chromosome (mom) and all of the DNA contained in the other chromosome. (Dad) What we create as a result of that replication is sister chromatids. Sister chromatids are identical copies of each homologous chromosome and they are held together by a centromere. Which of the following should contain DNA that is identical? Sister chromatids. (Remember DNA is not identical in homologous chromosomes)

Diabetic peripheral neuropathy (DPN) is a disease that can result when diabetes is not properly treated. This disease causes the destruction of neurons in the peripheral nervous system. One symptom of DPN is the loss of sensation in the hands and feet (for example, pain is not detected if the hand is placed on a hot burner). Which type of neuron(s) in the peripheral nervous system is/ are likely destroyed in someone with DPN to cause this symptom?

Sensory neurons

Chemotherapy side effects

Side effects include: Hair loss, digestive system upset (Small intestine epithelial cells and stomach cells have a high turnover rate which means these are going to be also targeted by chemotherapy drugs they won't be able to complete the cell cycle to produce more cells.) Altered taste Decreased immune function (So neutrophils, and eosinophils: they have a relatively short lifespan so in this case if chemotherapy is around they are not able to be created during cell division through the cell cycle; so we have decreased immune function during chemotherapy.) Bruising and bleeding (platelets: these fragments of cells that need to be replaced and created every roughly 10 days; so they have a very high likelihood of being impacted by the presence of chemotherapy drugs) Cancer treatments have improved the survival rates in the USA

Drug therapy and drug abuse

So many licit and illicit drugs act at the synapse. Botox for example, acts at the synapse by preventing neurotransmitters release. By preventing neurotransmitter release (we have prevented the cellular response) Which in the case of muscle, it was muscle contractions. (so by acting at the synapse drugs can often modulate communication between cells of the nervous system) Drugs at the synapse can include a couple of different modes of action: drugs can promote the action of neurotransmitters or increase the amount of neurotransmitters at the synapse. (drugs like benzodiazepines, alcohol, antidepressants and cocaine function in this way) Drugs can interfere with or decrease the action of a neurotransmitter. (Blocking its receptors for example caffeine does this) Drugs can replace or mimic a naturally occurring neurotransmitters. (So, They look and act just like a naturally occurring neurotransmitter. so when they are present the neurons respond exactly as they would as if a neuron before them has released neurotransmitter and is trying to communicate with them.) (examples, opiates and amphetamines act in this way.) All of these different modes function share the fact by acting at the synapse these drugs alter communication between the neurons. (They can either increase communication between neurons or decrease communication between neurons but they all change communication in someway)

Region of the central nervous system that is impacted by drug therapy and drug abuse (reward circuit)

The brain is made up of many interconnected circuits, (Groups of neurons that Synapse with one another) each responsible for coordinating and performing specific functions. One of the circuits (so one of these groups of neurons) this is called the reward circuit. The reward circuit reinforces positive behavior to increase the odds that we will repeat beneficial, pleasurable activities. The neurotransmitter dopamine is central to this. Ex: food, sex Many drugs of abuse increase signaling in this particular circuit. (Ex:cocaine) Tolerance often happens with both drug therapy (so licit drugs and drugs of abuse that are taken illicitly) Because essentially tolerance is the body's attempt to maintain homeostasis; By using negative feedback mechanisms. So, when the body detects that we have too much or too little of something it going to try to compensate for it. In this case when it detects that we have a lot of dopamine being release into this synapse, Tolerance develops because this is our bodies attempt to maintain homeostasis. well we have a lot of dopamine, So we should respond by decreasing the production of dopamine. So what happens is tolerance in this example, when we are looking at dopamine; the body responds by decreasing dopamine production where we would have fewer vesicles filled with less dopamine available for exocytosis. (But what happens with tolerance is in response to this elevated increase signaling and high-level of dopamine, Overtime we start to produce less dopamine which means that we need more drugs required to get the same response.) So it takes even more cocaine/drugs to increase the amount of dopamine that stays in the synapse to give us this increased pleasurable signal so that results and what we know as physiological tolerance.

Events at a synapse

The events of the synapse, when this neuron is actively signaling and needs to communicate with this next cell in line. 1. An action potential travels along the axon and reaches the axon terminal. (Brief reversal in our electrical charge that was traveling down the length of an axon, will arrive at the axon terminal) 2. Sending neuron (Presynaptic) it's going to cause these vesicles that are filled with neurotransmitters to undergo exocytosis. (The action potential arrives, it stimulates calcium to come in and that causes exocytosis; then those molecules (the neurotransmitters that are packaged in vesicles) are going to be placed outside of the cell (into the synaptic cleft) 3. The neurotransmitters then diffuse across the synaptic cleft (it's not far) So they are pretty close although not touching; Where the neurotransmitters are released and diffuse across the synaptic cleft. (So those neurotransmitters are going to go by diffusion where they were high, so when they were first released from that vesicles a whole lot of them, they are going to diffuse away and they will find their way ... 4. Receiving neuron/cell (postsynaptic) to receptor proteins in the membrane of the receiving cells. (Neurotransmitters bind to receptor proteins on the membrane of the receiving cell to elicit a response) Eliciting a response is highly variable depending on a few things: One, what kind of neurotransmitters are released? Two, what our receiving cell is

Neuron structure (cell body)

The first structure is the cell body. This contains the nucleus; so this is where we store genetic information. Also, the cell body contains all of the organelles that this cell needs to carry out its functions. (Example: ribosomes and endoplasmic reticulum for making proteins and things like mitochondria for producing ATP and generating energy. ( that's where you'll find the majority of these organelles is here and the cell body.)

Cancer cell characteristics (apoptosis)

The mutations that cancer cells accumulate give them unique characteristics not found in normal healthy cells. One of those characteristics is that they fail to undergo apoptosis. (In a cancer cell one of the characteristics is that there tumor suppressor proteins that normally stimulate apoptosis aren't functional.) So that means that there is no mechanism to destroy them to cell death through apoptosis; because the tumor suppressor proteins that encode for apoptosis functions don't work.

Axon damage

The myelin sheath also affects the ability of an axon to regenerate following damage. For example, if we have something that cuts or severs a nerve and breaks and disrupts the axons of the neurons within it. The neuroglia that form the myelin are different in the peripheral nervous system versus the central nervous system. So, the cells that actually make up this myelin, are two different varieties. In the peripheral nervous system, They are formed by Schwann cells. In the central nervous system they are formed by Oligodendrocytes. (The significant difference here, in the ability for regeneration comes from the fact that Schwan cells secrete chemicals and signals that can actually promote axon regeneration if this axon is damaged; so if a neuron is damage (the axon is severed, for example) the Schwan cells that are there to support that neuron can actually secrete chemicals to help that axon re-grow and to reform connections with its target tissue. Where as the oligodendrocytes, inhibits axon regeneration following damage. So, they secrete chemicals that prevent that neurons axon from regrowing. So, it will not be able to make new connections with its target tissue, if the axon was severed for example: and it's surrounded by oligodendrocytes.) Damage to axons of neurons in the central nervous system is more likely to be permanent and irreparable. (Oligodendrocytes Inhibit the axon for regenerating itself.) Axon damage in the peripheral nervous system is more likely to be repairable. (Schwann cells)

cell division

The normal process of one parent cell dividing to create two new identical daughter cells. This process is necessary for normal growth, development and to replace damage cells of the body. (So if we consider for example, human development, we all started as a single egg that was fertilized by sperm; in which, cell division allowed that single cell to divide and create two new identical daughter cells. Those each then divided and created 4 cells, those 4 cells divided to make 8 cells (etc) until you had millions of cells that made up you as an organism. Of course also continues through adulthood; so if you have damage or a wound for example, when you cut yourself, the cells around that damaged tissue are going to be undergoing cell division, dividing to create more cells to help replace those damage cells of the body and promote proper wound healing.) One important thing to consider, when we talk about cell division is that all new cells need a copy of the genetic material (DNA) When we talk about cell division, what that means is that each of those new cells that we get, we need to ensure has its own copy of genetic material (recipe book) so that it knows which proteins it needs to produce, how to produce them and that the new cells can carry out their functions. We need a mechanism to ensure that we have an orderly way to copy our DNA and we have an orderly way of making sure that each new daughter cell has it on complete copy; so all of the genes in this original cookbook are going to be passed on to both of those daughter cells.

Control of the cell cycle (checkpoints)

The other way that we can control the cell cycle is by controlling it's progression through the individual phases of the cell cycle. So controlling the movement of a cell from G1 into S, And then from G2 into mitosis, and then proceeding through mitosis. (controlled by proteins that form checkpoints) The important point of this mechanism of control is : Telomeres that control how many times a cell can divide and checkpoints which controls movements of the cell through the cell cycle are important because if they fail, this can result in unrestricted growth and cancer. (so either cells that can divide too many times(telomeres)or cells that can move through these phases to rapidly without any mechanism to stop them. (Checkpoint)

Two types of cells found in the nervous system

The primary cells that's responsible with actual communication is neurons. Neurons are the cells of the nervous system that will actually transmit information within the nervous system. The other types of cells that we find in the nervous system (that actually out numbers neurons about 10 to 1) is what's known as neuroglia. Neuroglia are cells that don't actually do any of the communication; (so they are not actually transmitting information about touch or about movement for example) but they are responsible instead for supporting and nourishing the neurons.

Individuals often develop tolerance to caffeine. Initially they feel alert after one cup, but over time they find it takes 3 or 4 cups to achieve the same effect. Which of the following explains this phenomenon?

There are an increased number of adenosine receptors on neurons

Antidepressants

They affect reuptake transporters such as Paxil and Prozac. They affect the level of serotonin in synapsis so depression can result in signaling between neurons in circuits of the brain that signal mood and emotion decreases. Often due to a reduction in the release of the serotonin neurotransmitter. So in this case, these individuals have less serotonin being released to begin with. (In the synaptic cleft)So to help alleviate the symptoms antidepressants block the transport proteins that remove serotonin from the synapse. So we don't have as much being released, but we prevent it from being removed - then at least what is there can hang out in the synapse longer, can bind to its receptor and can elicit its cellular response to help modulate mood and emotion. So with antidepressants, serotonin remains in the synapse longer, and we can increase signaling and alleviate some of the symptoms using a similar mechanism of blocking transport to increase the time spent in the synaptic cleft.

Synapse

This is where sending neurons axon is in close proximity (but not touching) a receiving cell. A receiving neuron can be another neuron (so for example, a sensory neuron communicating with an interneuron) or an effector, like a muscle; so if this was a motor neuron that needs to communicate with a muscle there's a synapse (a space) between the end of that neurons axon and then the receiving cell. The axon terminal is the region at the end of the sending axon. (Some axons will branch off at the end so there could be several axon terminals , so it can form several synapses with the same cell or with multiple cells. (so it could have synapses with other neurons as well, and that's our ending region.) - The synaptic cleft is the physical space between the sending and the receiving cells. (Sending cell is known as the presynaptic neuron, so presynaptic mean before the synapse.) Receiving cell is known as postsynaptic neuron/cell (after the synapse) So, this is the physical space between the presynaptic and postsynaptic cells. * The chemical that's released that's going to traverse the space is called a neurotransmitter; and it's stored in vesicles that stay in the axon terminal waiting for the arrival of an action potential.

treatment for cancer

Treatments of cancer is highly variable but generally depends on whether or not cells have remained localized or have metastasized (entered the circulatory system and gone to a location other than their site of origin.) Surgery is essentially physically removing cancerous cells from the body. So, going into a location and removing a localized tumor. (Treats localized cancer) Radiation is generally radiation waves that are directed at a cancerous growth. And these are meant to disrupt the cell cycle; therefore preventing rapidly dividing cells from being able to divide any further. (Treat localized cancer) Chemotherapy is unique because it introduces drugs that disrupt the cell cycle into the circulatory system, (Given orally or by IV) So they go throughout the body, and they function by impacting rapidly dividing cells, so that those cells can no longer divide further. All of these forms can be used in conjunction with each other to treat cancer. Like radiation and surgery can be used together for example. ONLY Chemotherapy would be useful to treat cancer that was/is metastasized!!!

Resting potential

What's happening when a neuron has not detected any changes, and does not have anything to communicate. (The neuron is at rest, not detecting any stimuli.) Neurons are said to be at the resting potential; This means that they are not actively conducting a nerve impulse or a signal. But neurons are never truly at rest; many cellular functions are always happening including: running the sodium potassium pump (which is also known as the Na-K AT Pase) This is a protein that is embedded in the membrane and it's moving charge sodium ions (Na+) and potassium ions (K+) across the plasma membrane using active transport. (This is happening at rest) Sodium ions and potassium ions are moving from a low concentration to a high concentration gradient (using a protein carrier); ALOT of energy is required (ATP) So, in all neurons at rest, the sodium potassium pump is constantly utilizing energy in the form of ATP to move three sodium ions out of the cell and move 2 potassium ions into the cells. (Moves them in opposite directions) — Once this active transporter transport sodium out and potassium in; they are stuck outside and inside the cell right at this moment because unless they have another protein to help them cross the membrane, they are not permeable to the phospholipid bilayer. Considering the action of the sodium potassium pump, the inside of the cell will become more negative relative to the outside. (Imbalanced) The sodium potassium pump creates the following conditions: 1. It creates a high concentration of sodium ions outside of the cell 2. Creates a high concentration of potassium ions inside the cell 3. Because we have this imbalance with the ions (three positives out & two positives in) we also have the inside of the cell becoming more negative relative to the outside. Resting potential typically has a value of about -70 mV So what's happening and resting potential? 1. At resting potential, our sodium potassium pump generates concentration gradient and contributes to negative charges inside the cell. 2. We have a high concentration of sodium ions outside and a high concentration of potassium ions inside 3. Channels for facilitated diffusion are closed (Sodium is stuck outside while potassium is stuck inside the cell) 4. Now when the neuron is stimulated, instead of a resting potential now we are going to be generating action potential's. We're going to use the movement of these ions to briefly change the charge of our membrane.

proto-oncogenes (mutations)

When proto-oncogenes mutate they become cancer causing genes called oncogenes. (Oncogene is defined as a proto-oncogene that has undergone a mutation.) Proteins that were coded by our proto-oncogene, stimulated progression through the cell cycle only when the cell was supposed to divide. (When we have a mutation in a proto-oncogene (that makes an oncogene) These stimulate the cell cycle all of the time, regardless of whether or not the cell is supposed to divide. so, even if it is not receiving environmental cues to divide (for example, receiving environmental cues to divide when we cut our skin and we need to repair and replace those damage cells.) These cells that have these mutations (oncogenes) these will make proteins that over stimulate the cell cycle. so these constantly tell the cell to go through division, divide, create more cells even though the cell is not supposed to be; because it is not receiving a cue to divide. That is what's abnormal about the proteins encoded for by an oncogene. (They can't carry out the same function that the proteins encoded for by proto-oncogenes could.) A mutation in a proto-oncogene, (creates an oncogene) this new protein causes continual cell division. so not just when the conditions are appropriate but all of the time; it keeps being stimulated to go through each of the checkpoints to proceed through the cell cycle and divide and create more cells.

Which of the following is TRUE of channels for facilitated diffusion of sodium ions (Na+)?

When they open the inside of the cell becomes more positive

Caffeine

adenosine is an inhibitory neurotransmitter use throughout the central nervous system. So adenosine is going to prevent neurons from signaling. So adenosine is going to prevent action potentials from occurring which is important to slow down neural activity (adenosine is usually associated with when we need to sleep.) Adenosine is released so that neurons can start to not have action potential's A lot of neurons (not all) will cease activity, so that we can slow neural activity and we can induce sleep because of adenosine release. When caffeine is around it binds to the adenosine receptors and blocks them. Supposed to be on the receiving cells (on postsynaptic neuron's in the central nervous system) Can't bind adenosine because the receptor is blocked by caffeine. (Caffeine basically just sits there and blocks adenosine from being able to bind into it, preventing sleeping) What happens is this receiving cell that supposed to be inhibited to slow neural activity, can't be inhibited.) Tolerance with caffeine, (again tolerance is our body's attempt to maintain homeostasis with negative feedback) Overall, they will create more receptors so suddenly now your body responds by adding more adenosine receptors. Now the problem is that If you have caffeine that you had before to block these three initial receptors, it is not sufficient to block all these new receptors. so adenosine can still find these new receptors and you go back to feeling sleepy. so tolerance with caffeine develops because more receptors means that you need more caffeine to block them. so instead of one cup of coffee now you need to cups of coffee to feel awake or 3 cups of coffee because you have more receptors making you feel sleepy. More receptors = more caffeine needed to block them.

The cell cycle

cell division is only one part of the process of cell cycle. The cell cycle leads to a series of events that take place in a cell, leading to duplication of its contents (example DNA) and division of those contents to create two new cells. The process of interphase followed by mitosis and then cytokinesis to give us these two new daughter cells. Interphase (The largest phase of the cell cycle) During interphase the cell is caring out it's normal functions (So, for example if it's a muscle cell is going to be carrying out the function of movement. And if it's a neuron it is carrying out communication etc.) And it is preparing for division incase it has to make new cells. During mitosis, this is where we have division of the genetic material. (DNA) (Actually divvying up DNA, making sure that each of our new cells that we are creating has its own exact copy of the DNA that are parent cells started out with. The last phase of the cell cycle is known as Cytokinesis, this is where we actually split the cell in half and this is where we actually have a division of the cell and all of its contents to create our two new cells. (Each of these new cells Simply will go back right to the beginning of the cell cycle (Interphase) and can repeat this process all over again; If and when they need to divide.) How frequently cells go through this entire cycle is highly variable depending on their function and location in the body. (some cells can spend more time in interphase carrying out there normal function, other cells carry out their normal function, But then they need to divide very frequently and go through mitosis and cytokinesis and go through this entire cell cycle way more often than other cells. The following is the typical lifespan of different cells of the body. This is how long a cell functions optimally before it is damaged or destroyed. Which type of cells would you expect to go through this entire cell cycle more frequently? (Cells lining the stomach) Because it is being damaged and destroyed (more frequently) which means it needs to go to the cell cycle more rapidly to replace those lost and damaged cells; compared to something like a fat cell (they can persist for eight years before it needs to be replaced) So anything that gets destroyed or damaged the quickest; will have to go through the cell cycle more frequently.

Carcinogenesis

development of cancer; can be divided into three phases. Initiation: (the first phase of cancer development) where a cell has a mutation that causes it to divide excessively. As it divides excessively, the more that it divides the more likely it is to accumulate mutations. (As cells divide, the more likely they are to be making mistakes when they're copying DNA for example; so instead of this one mutation it starts to accumulate more mutations.) As this phase progresses, cells also typically lose whatever their normal function was. (Loss of function) Promotion: (second phase) where cells form a mass (tumor) and additional mutations continue to accumulate. (A larger cluster) Progression (the last phase) this is where one cell develops a mutation that gives it an advantage over other cells, and can invade surrounding cells. (Invasive tumor) (Can move into surrounding tissues for example) Progression can ultimately lead to metastasis. Metastasis happens if those cells reach a blood vessel or lymphatic vessels; what happens is if they reach either of these, the lymphatic vessels will carry it to the lymph system (which will drain it into the circulatory system) or this blood vessel would introduce it to the circulatory system; as soon as the cell enters either one of those that cell can now be transported throughout the body. (So, it enters the circulatory system, lodges in a new location and forms a new tumor at a distant location, (so that metastatic cancer. A malignant tumor.)

Benzodiazepines (Anxiety drugs)

illicit drugs that affect inhibitory neurotransmitter's. So some examples: Xanax and Valium These function by increasing the opening of some neurotransmitter receptors that are inhibitory. (Remember inhibitory meant that when these neurotransmitters bind to the receptors, they cause the cells to become more negative. so instead of being more likely to have an action potential; it is less likely to have an action potential) Benzodiazepines Increase this effect so they increase the opening of these inhibitory neurotransmitter's which are usually leading potassium leave the cell by facilitated diffusion, sometimes there's also other ions that can flow to cause a cell to become more negative; but these are essentially driving the cells membrane to become more negative so it's less likely to have an action potential. So these prevent action potential's in neurons within circuits of the brain that usually signal when fear or stress are present. So normally these circuits of the brain would have action potential's to help signal that information but by having benzodiazepines around, essentially what you're doing is quieting down those neurons (they are inhibited) and are less likely to fire action potential's which means they don't signal that fear or that stress signal.

Mutation

results from a permanent change in the DNA sequence of a gene. (If we mutate/change the instructions of the DNA, we are essentially creating a different recipe (gene) which will call for different ingredients (amino acids) and now we will end up with a different (cake) protein. Most mutations are harmless; the protein made still functions as it should. (In this case, a silent mutation means that there is a change in our DNA, But luckily, that change coded for amino acids (ingredients) are very similar to the original amino acid; so that we are able to still make a protein that functions very similar to the original. So a silent mutation will be in example of a mutation that causes a change and maybe the change (if we think of it in terms of our cooking analogy; so a silent mutation will be changing one of our ingredients from milk to cream) slightly different ingredient but still very similar in its overall product. (So, a slightly different protein is created but it's still similar to the original protein and as a result, The protein that we end up making is very similar and can still carry out the same functions as the original protein.) When we are unlucky some of our mutations are harmful; the protein meat is drastically changed and it no longer functions properly. (So in this case, instead of substituting one amino acid for another that's very similar, these types of mutations substitute one amino acid for another that is very different and we end up with a protein as a result that's very different. (So again, thinking about our cooking analogy, in this recipe we are trying to make a cake, but instead of using milk, we insert and substitute (a very different ingredient) carbonated soda. Now we are going to produce a very different cake (protein) and in this case this protein will no longer carry out it's regular function.)

myelin sheath

the myelin sheath (the blue structure that's covering the axon) covers the axon of many neurons (not all neurons has this) Made of Neuroglia who cells that support and nourish neurons will form this myelin sheath. (Essentially wrapping their lipid membrane around the axon to help it with signaling.) Myelin sheath only covers a portion of the axon. (It's myelin then a gap, myelin then another gap and the pattern continues.) the gaps are known as nodes of ranvier. these nodes of ranvier are going to be important for helping the axon to communicate much more rapidly. The presence of myelin, so if a neuron has myelin around its axon- it increases the speed of nerve impulse conduction and it permits really rapid communication within and between neurons. So If an axon is myelinated, The signal (this nerve impulse) will move much more rapidly down the length of the axon, and it's going to be able to communicate faster within that neuron, So we are going to be able to get that signal from the dendrites down the axon much quicker and we're gonna be able to communicate with the next cell in line much faster if there is myelin present.

Exocytosis (outside the cell)

transports large molecules outside the cell via the fusion of a vesicle with the plasma membrane.