Physiology nervous system, neurons and synapse

Function of Dopamine in the brain

-Insufficient dopamine biosynthesis in the dopaminergic neurons can cause Parkinson's disease (in which a person loses the ability to execute smooth, controlled movements) -attention deficit disorder (prefrontal cortex) -Regulating prolactin secretion (Dopamine produced by neurons in the arcuate nucleus of the hypothalamus) -Dopamine is commonly associated with the pleasure system of the brain. Dopamine is released (particularly in areas such as the nucleus accumbens) - abnormally high dopamine action apparently leading to these conditions (schizophrenia)

Norepinephrine

-It is released from the adrenal medulla of the adrenal glands as a hormone into the blood -but it is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons during synaptic transmission. -As a stress hormone, it affects parts of the human brain where attention and responding actions are controlled. Along with epinephrine, norepinephrine underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing skeletal muscle readiness.

Ependyma

Form a single layer of cuboidal cells lining the central cavities of the brain and spinal cord. They have microvilli also.

Characteristics of a neurotransmitter

1- presence of the substance within neuron terminals 2- release of the substance with neuronal stimulation 3- application of the exogenous substance to the postsynaptic membrane produces the effects of stimulation of the presynaptic neuron. 4- the concentration -response curve of the substance applied to the postsynaptic membrane is affected by drugs in a similar way as normal postsynaptic response. 5- a local mechanism exists for inactivation of the substance (e.g.: enzymatic degradation, uptake into nerve terminal or glia).

Function of the BBB

1.It maintains a constant environment for neurons in the CNS and protects the brain from endogenous or exogenous toxins. 2.It prevents the escape of neurotransmitters from their functional sites in the CNS into the general circulation. 3.Drugs penetrate the blood-brain barrier to varying degrees. For example, nonionized (lipid-soluble) drugs cross more readily than ionized (water-soluble) drugs. 4.Inflammation, irradiation, and tumors may destroy the blood-brain barrier and permit entry into the brain of substances that are usually excluded (antibiotics. radiolabeled markers). For example, L-DOPA, the precursor to dopamine, can cross the BBB, whereas dopamine itself cannot. (e.g., Parkinson's disease)

Tumors of Neuroglia (glioma)

Account for about 50% of intracranial tumors. Astrocytomas and glioblastomas are tumors of astrocytes. Gliomas apart from ependymomas are very invasive and grow large with minimal effect on neighboring neurons.

Inhibitory

An Inhibitory Postsynaptic Potential (commonly abbreviated as IPSP) is the change in membrane voltage of a postsynaptic neuron which results from synaptic activation of inhibitory neurotransmitter receptors. The most common inhibitory neurotransmitters in the nervous system are GABA and glycine.

Comparison of cerebrospinal fluid (CSF) and blood concentrations

CSF=Blood: Na+, Cl-, HCO3-, Osmolarity CSF< blood: K+, Ca2+, Glucose, Cholesterol, Protein CSF> blood: Mg2+, Creatinine

Characteristic of neurons

Conduct electrical impulses along the plasma membrane Produce nerve impulse Produced action potential Longevity: can live and function for a lifetime Do not divide: fetal neurons lose their ability to undergo mitosis High metabolism rate: requires abundant oxygen and glucose

Cells of neuron system

Densely packed and intertwined Neurons: transmit electrical signals, found in gray matter of CNS and ganglia Neuroglial cells (support cells): non-excitable, surround and wrap neurons Neurons are basic structural unit of the nervous system and possess a cell body and processes called neurites The human body contains billions of neurons

Amino acids

Excitatory neurotransmitters an excitatory postsynaptic potential (EPSP) is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell. They are the opposite of inhibitor postsynaptic potentials (IPSPs), which usually result from the flow of negative ions into the cell. A postsynaptic potential is defined as excitatory if it makes it easier for the neuron to fire an action potential. The neurotransmitter most often associated with EPSPs is the amino acid glutamate, and is the main excitatory neurotransmitter in the central nervous system.

Gliosis and glial scar

Gliosis is hyperplasia and hypertrophy of astrocytes that occur in reaction to CNS injury. Oligodendrocytes: respond to injury by expanding and vacuolation of their cytoplasm.

Neurotrophins

In a developing fetal brain, chemicals called neurotrophins promote neuron growth: -Nerve growth factor (NGF) -Brain-derived neurotrophic factor (BDNF) -Glial-derived neurotrophic factor (GDNF) -Neurotrophin-3(it is important in the embryonic development of sensory neurons and sympathetic ganglia.)

Dopamine

In the brain, dopamine functions as a neurotransmitter, activating the five types of dopamine receptor - D1, D2, D3, D4 and D5, and their variants. Dopamine is produced in several areas of the brain: -Substantia nigra -Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary. -Dopamine can be supplied as a medication that acts on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. -dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. -To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease L-DOPA (levodopa), which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.

Structure of a neurons (axon)

Long portion Transmit impulses away from neurons Only 1 axon No protein synthesis in axon No nissl bodies in axoplasm Initial segment: after axon hillock, most excitable side, origination site of action potential Neurofilaments, microtubules and actin microfilaments are present Is smooth without any synapse Axon terminal (buttons)

Nitric oxide and carbon monoxide

NO is one of the few gaseous signaling molecules known. It is a key biological messenger, playing a role in a variety of biological processes. Nitric oxide, known as the 'endothelium-derived relaxing factor is biosynthesized from arginine and oxygen by various nitric oxide synthase (NOS) enzymes and by reduction of inorganic nitrate. The endothelium (inner lining) of blood vessels use nitric oxide to signal the surrounding smooth muscle to relax, thus dilating the artery and increasing blood flow. The production of nitric oxide is elevated in populations living at high-altitudes, which helps these people avoid hypoxia. Effects include blood vessel dilatation, neurotransmission, modulation of the hair cycle, and penile erections.

Neuropeptide Y

NPY is a 36 amino acid peptide neurotransmitter found in the brain and autonomic nervous system. It augments the vasoconstrictor effects of noradrenergic neurons. NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy. It forms part of the "lipostat" system along with leptin and corticotropin-releasing hormone (CRH).

Synapses

Nervous system consists of neurons that are linked together to form functional conducting pathways. Synapses are the sites where two neurons come into close proximity. The term also implies to the nerve-muscle contact as well. Various forms: Axodendritic, axosomatic and axoaxonic. The first two are the most common forms. Axons can have a terminal expansion or a series of expansions called bouton de passage which make several contacts as they pass through a dendritic tree. Types of synapses: 1- Chemical (most common) 2- Electrical

Action of neurotransmitters

Neurotransmitters are released from the nerve endings after the nerve being stimulated (arrival of action potential). This results in an influx of Ca++ ions into the presynaptic part which causes the synaptic vesicles to fuse with the presynaptic membrane. The neurotransmitters are then released into the synaptic cleft, increasing or decreasing the resting potential of the postsynaptic membrane for a short time. The receptor on postsynaptic membrane binds the neurotransmitter which opens the ion channels, generating an excitatory postsynaptic potential (EPSP) e.g.: in case of Ach in nicotinic receptors or inhibitory postsynaptic potential (IPSP) in case of GABA for example. Other receptors bind the neurotransmitter and activate a 2nd messenger system such as a G-protein (response lasts for minutes). Examples: Ach (muscarinic), serotonin, neuropeptides and adenosine (neuromodulators).

Fate of the neurotransmitters

Neurotransmitters effect for a short time since they are either destructed in the cleft or reabsorbed by the presynaptic part (e.g.: Ach in the synaptic cleft is destructed by Acetylcholinesterase (AChE). In case of Catecholamines, the effect is limited by their return to the presynaptic ending.

Neurological clinical tips

Parkinson could be Treated to some extent by neurotransmitters. Dopamine can not cross the BBB. L-dopa can cross BBB. Synaptic blocking agents: transmission of nerve impulses is due to release of neurotransmitters into synaptic cleft, activating the postsynaptic membrane. Transmission can be easily blocked; long chain neurons with multiple synapses are easier to block. General anesthetics block synaptic transmission. Local anesthetics block nerve conduction when applied locally; by interfering with the transient increase in permeability of the axolemma to Na+, K+ and other ions. Small nerve fibers are more sensitive and slower to recover. Phenothiazines block Dopamine receptors postsynaptically.

Structure of neuron (cell body)

Perikaryon Size varies from 5-140 µm Has normal cell organelles Nissl bodies (rER) Neurofibrils and lipofuscin

Supporting cells

Provide supportive functions for neurons cover nonsynaptic regions of the neuron Two types in peripheral NS: Schwann cells (form myelin sheaths around perIpheral axons) and satellite cells (ganglionic gliocytes; support neuron on cells bodies within the ganglia of the PNS) 4 types (neuroglial cells) in central NS: Oligodendrocytes (form myelin sheaths around axons of the CNS), Microglia (migrate through the CNS and phagocytose foreign and degenerated material), astrocyte (help to regulate external environment of neurons in the CNS), Ependymal cells (line the ventricles of the brain and the central canal of the spinal cord)

Structure of neuron (dendrite)

Shorter portion Increases neurons receptive area Transmits impulses toward the neuron Nissl bodies in it's basil parts

Microglia

Smallest among neuroglial cells. Migrate into the nervous system in fetal life. They are scattered in the CNS. Functions: In the normal CNS, they are inactive (resting microglia) but, in inflammation or degeneration of CNS, they proliferate and become active and phagocytic.

Oligodendrytes

Supporting cells Small cell bodies no filaments and their cytoplasm one oligodendryte can mylinate many fibers, not surrounded by a basement membrane unlike the Schwann cells and PNS Function is Myelination in the CNS Olis that surround nerve cell bodies may influence the biochemical environment of neurons

Neurotransmitters

The presynaptic vesicles contain the neurotransmitter substance and the mitochondria provide ATP for neurotransmitter synthesis. Acetylcholine (Ach), norepinephrine, epinephrine, dopamine, glycine, serotonin, gamma-aminobutyric acid (GABA), enkephalines, substance P and glutamic acid Ach: is found at neuromuscular junction, in autonomic ganglia, parasympathetic nerve, Norepinephrine: found at sympathetic nerve endings, in CNS: in hypothalamus. Dopamine: found in high concentrations in basal ganglia and hypothalamus. Glycine: is found principally in synapses in the spinal cord. Glutamate: is an excitatory amino acid neurotransmitter in many central nervous neurons.

Multiple sclerosis (Demyelinating diseases of the CNS)

Unknown disease, occurs between ages of 20 to 40 years, demyelination in CNS, usually starts with optic nerve, spinal cord, and cerebellum. Axonal degeneration as a result of demyelination and/or early in the course of the disease is part of the disability.

Regeneration of a Cut axon

When an axon in peripheral nerve is cut, the distal portion of the axon that was severed from the cell body degenerates and is phagocytosed by Schwann cells. The schwann cell, surrounded by the basement membrane, then form a regeneration tube, as the part of the axon that is connected to the cell body begins to grow and exhibit amoeboid movement. The SC secrete chemicals that attract the growing axon tip, and the regeneration tube helps to guide the regeneration axon to its proper destination. In CNS, Regeneration is more limited , due in part to the absence of a continuous neurilemma (as is present in the PNS), which to inhibitory molecules produced by oligodendrocytes and astrocytes in the injured CNS.

Serotonin

a master neurotransmitter, is manufactured from tryptophan. It is found all over the body and is necessary to modulate the levels of the stress hormones. In the central nervous system, serotonin is believed to play an important role in the regulation of anger, aggression, body temperature, mood, sleep, vomiting, sexuality, and appetite. Low levels of serotonin may be associated with several disorders: -namely increase in aggressive and angry behaviors -clinical depression -migraine -bipolar disorder, anxiety disorders If neurons of the brainstem that make serotonin—serotonergic neurons—are abnormal, there is a risk of sudden infant death syndrome. Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier.

Chemical synapses

involve the neurotransmitters released from a pre-synaptic neuron that becomes attached to a protein (receptor) at post-synaptic membrane. Chemical synapses are unidirectional. Ultrastructure of chemical synapses The opposed surfaces of terminal axonal expansion and the neuron are termed the presynaptic and postsynaptic (with sub synaptic web) membranes, respectively, and are separated by a synaptic cleft (20- 30nm). Membranes are thicker here. Presynaptic cytoplasm contains vesicles, mitochondria and lysosomes among others. On postsynaptic side, the cytoplasm contains parallel cysternae. Synaptic cleft contains polysaccharides.

Myelin sheath

myelin sheaths of the CNS are formed by oligodendrocytes. This process occurs mostly postnatally. Showann cells form the myelin sheaths of PNS Unlike a Schwann cell, which forms a myelin sheath around only one axon, each oligodendrocyte has extensions, form myelin sheaths around several axons. The myelin sheaths around axons of the CNS give this tissue a white color, areas of the CNS that contain a high concentration of axons thus form the white matter. The gray matter of the CNS is composed of high concentrations of cell bodies and dendrites, which lack myelin sheaths.

Electrical synapses

no chemical transmitters. Gap junctions formed by specialized channels called Connexons. Each Connexon consists of 6 parts called Connexins. These channels are from cytoplasm of the presynaptic neuron to that of the postsynaptic neuron which allow the flow of ionic current between cells with minimal delay. These are found in a group of neurons performing an identical function. These are bidirectional.

Astrocytes

small cell body, numerous branching processes Many astrocytic processes are interwoven at inner and outer surfaces of CNS, forming outer and inner glial limiting membranes. Functions: 1- They form a supportive framework for neurons, and in embryo they serve as a scaffolding for migration of immature neurons. 2- they cover the synaptic contacts between neurons and thus insulate axon terminals from influencing neighboring unrelated neurons. 3- They absorb glutamate (transformed into glutamine) and GABA secreted by the nerve terminals, thus limiting the influence of these neurotransmitters. 4- They absorb excess K+ of extracellular fluid. Since K+ diffuses out of neurons during the production of nerve impulses, for maintaining the proper ionic environment for neurons. 5- By feet surrounding blood capillaries take up glucose from the blood, the glucose metabolized into lactic acid, is then released and use as an energy source by neurons. 6- Phagocytosis of degenerated axon terminals. 7- replacement gliosis: when neurons die due to disease or injury, they proliferate and fill the spaces previously occupied by neurons. 8-Astrocytes induce the formation of the blood-brain barrier. 9- produce trophic substances for neurons.

Blood-Brain Barrier (BBB)

the barrier between cerebral capillary blood and the CSF. CSF fills the ventricles and the subarachnoid space. -It consists of the endothelial cells of the cerebral capillaries and the choroid plexus epithelium. Formation of CSF by the choroid plexus epithelium Lipid-soluble substances (CO2 and O2) and H2O freely cross the blood-brain barrier and equilibrate between blood and CSF. Other substances are transported by carriers in the choroid plexus epithelium. They may be secreted from blood into the CSF or absorbed from the CSF into blood Protein and cholesterol are excluded from the CSF because of their large molecular size The composition of CSF is approximately the same as that of the interstitial fluid of the brain, but differs significantly from blood CSF can be sampled with a lumbar puncture