PSYC326_Chapter 15

Disorders of development: inherited metabolic disorders

"Errors of metabolism": genetic abnormalities in which the recipe for an enzyme is in error - the enzyme cannot be synthesized. If the enzyme is a critical one, the results can be very serious.

Cerebrovascular accidents: treatment - after a stroke occured

1. Administration of drugs that block factors present in the brain that inhibit axonal growth 2. Activating the brain's intrinsic neural growth factors 3. Reducing swelling and inflammation Drugs 1. NogoA: myelin protein that inhibits the branching and growth of axons - Injection of antibodies against NogoA can increase recovery from brain damage 2. Inosine: naturally occurring chemical - Administration activates a protein that encourages axon growth Physical therapy - Physical therapy and sometimes speech therapy - Exercise and sensory stimulation can facilitate recovery from the effects of brain damage

Tumors and seizures: seizures - treatment

1. Anticonvulsant drugs: increasing the effectiveness of inhibitory synapses - increasing inhibition via GABAergic synapses - Response is good - sustain a high quality of life 2. Brain surgery: remove region of brain surrounding the focus when it cannot be treated by drugs.

Disorders caused by infectious diseases

1. Bacteria 2. Fungi 3. Parasites 4. Viruses Answer to one of the test questions is virus - Due to the majority of meningitis encephalitis

Tumors and seizures: seizures - overview of classification

1. Generalized seizures (with no apparent local onset) - Tonic-clonic (grand mal) - Absence (petit mal) - Atonic (loss of muscle tone; temporary paralysis) 2. Partial seizures (starting from a focus) - Simple (no major change in consciousness) - 1) localized motor seizure, 2) motor seizure, with progression of movements as seizure spreads along the primary motor cortex, 3) sensory (somatosensory, visual, auditory, olfactory, vestibular), 4) psychic (forced thinking, fear, anger, etc.), 5) autonomic (e. g., sweating, salivating, etc.) - Complex (with altered consciousness) Includes 1-5, as above 3. Partial seizures (simple or complex) evolving to a generalized seizure: Starts as simple partial seizure or a complex partial seizure, then becomes a grand mal seizure

Tumors and seizures: tumors - treatments

1. Radiation: some tumors are sensitive to radiation. They can be destroyed by a beam of radiation. 2. Surgery: some tumors can be removed by surgery. 3. Chemotherapy: some brain tumors respond to chemotherapy, with or without radiation or surgical interventions. - Causes rapidly dividing cells to die by interfering with their DNA replication

Tumors and seizures: seizures - causes

1. Scarring: most common cause. Produced by: injury, stroke, developmental abnormality, or irritating effect of a growing tumor. - After a head injury, development of seizures can take a while - head injury from a vehicle accident will not have a seizure until several months later 2. Genetic factors: incidence of seizure disorders - Nearly all of the genes that have been identified as playing a role in seizure disorders control the production of ion channels. Ion channels control the excitability of the neural membrane and are responsible for the propagation of action potentials - Most seizure disorders are caused by nongenetic factors 3. Drugs and infections that cause a high fever can produce seizures. - High fevers are most common in children, and ~3% of children <4 years get seizures associated with fevers 4. Sudden withdrawal from chronic alcohol, barbiturate, and benzodiazepine use - Sudden release from the inhibiting effects of the drug leaves the brain in a hyperexcitable condition - can be fatal - Substituting a longer-acting drug and gradually reducing the amount of drug used can reduce the likelihood of seizures during withdrawal from sedative drugs.

Cerebrovascular accidents: causes - excitotoxicity - process

1. When blood to a region of the brain is interrupted, the oxygen and glucose in that region quickly deplete - Sodium potassium transporters (regulate the balance of ions inside and outside the cell) and other cellular mechanism, stop functioning. 2. Neural membranes become depolarized -> causes release of glutamate - Activation of glutamate receptors increases the inflow of sodium ions and causes cells to absorb excessive amounts of calcium through NMDA channels 3. Presence of excessive amounts of sodium and calcium within cells is toxic 4. Intracellular sodium causes the cells to absorb water and swell. - Inflammation attracts microglia and activates them, causing them to become phagocytic 5. Phagocytic microglia begin destroying injured cells 6. Inflammation attracts white blood cells - adhere to the walls of capillaries near the ischemic region and obstruct them - Presence of excessive calcium in the cells activates calcium dependent enzymes - destroy molecules that are vital for normal cell functioning 7. Damaged mitochondria produce free radicals (molecules with unpaired electrons that act as oxidizing agents) - Free radicals: extremely toxic; destroy nucleic acids, proteins, and fatty acids.

Disorders of development: toxic chemicals - alcohol

Alcohol: exposes the fetus to alcohol. It easily passes the placenta - Fetal exposure in 3rd or 4th week of gestation - One drink is enough to cause problems. There is no threshold dose, there are problems with any level of alcohol you drink Alcohol disrupts typical brain development by interfering with a neural adhesion protein (protein that helps to guide the growth of neurons in the developing brain) - Direct effects on neural plasticity - Alters the development of neuronal stem cells and progenitor cells Fetal alcohol syndrome: birth defect caused by ingestion of alcohol by pregnant woman. Abnormal facial development and impaired brain development related to prenatal alcohol exposure - Disrupts neural adhesion protein - important for nerve growth and establishing good connections in the brain

Degenerative disorders: multiple sclerosis

Autoimmune demyelinating disease. Immune system attacks myelin sheaths, leaving behind hard patches of debris called sclerotic plaques. - Scar tissue occurs at scattered locations within central nervous system. Damage occurs in white matter located throughout the brain and spinal cord - Wide variety of neurological symptoms are seen - Symptoms: cognitive disfunction Often diagnosed by the patient Remitting-relapsing MS: ymptoms often appear, increase in intensity and then decrease, to be followed by another increase in symptoms after varying periods of time. Progressive MS: characterized by a slow, continuous increase in the symptoms of the disease. - Remitting-relapsing MS is followed by progressive MS later in the course of the disease

Degenerative disorders: transmissible spongiform encephalopathies

Bovine spongiform encephalopathy (BSE/"mad cow disease"): a fatal contagious brain disease whose degenerative process gives the brain a spongelike (or Swiss cheese-like) appearance Diseases include: 1. BSE: can be transmitted to humans and produces a variant of Creutzfeldt- Jakob disease 2. Creutzfeldt-Jakob disease: PRPN-p gene on chromosome 20 (codes for the human prion protein gene). Causes dysfunction in the cerebral cortex 3. Fatal familial insomnia: causes dysfunction in the thalamus. People stay up too long and in less than a year they will die 4. Kuru: causes brain cells to be killed. Found in tribes in New Guinea - Degeneration of the cerebellum in this disorder - Members of indigenous groups in ate their brains and sometimes contracted the disease from diseased tribe members - Women and children would eat the brains of the individuals - Fearful, losing coordination, leading to death in the individuals 5. Scapie: brain stem disorder. It was originally only found in goats and sheep. 6. Chronic wasting disease: problem in the brain stem. Seen most in elk and deer. Cannot take care of themselves, don't eat

Tumors and seizures: seizures - consequences

Brain damage - ~50% of patients with seizure disorders show evidence of damage to the hippocampus. Amount of damage is correlated with the number and severity of seizures Significant hippocampal damage can be caused by a single episode of status epilepticus (relatively rare condition - patient undergoes a series of seizures without regaining consciousness) - Damage: caused by an excessive release of glutamate during the seizure - can cause glutamate excitotoxicity

Degenerative disorders: Parkinson's disease - brain

Brains: near-disappearance of nigrostriatal dopaminergic neurons - Many surviving dopaminergic neurons show Lewy bodies Lewy bodies: abnormal circular structures found within the cytoplasm Akinesia: difficulty in initiating movements - Associated with decreased activation of the supplementary motor area Tremors: abnormalities of a neural system involving the pons, midbrain, cerebellum, and thalamus

Degenerative disorders: Parkinson's disease

Caused by degeneration of the nigrostriatal system—the dopamine-secreting neurons of the substantia nigra that send axons to the basal ganglia Deficiency of automatic, habitual responses caused by damage to the basal ganglia Causes a poverty of movements Primary symptoms: muscular rigidity, slowness of movement, a resting tremor, and postural instability - Once they are seated, they find it difficult to rise - Once they begins walking, they have difficulty stopping Other symptoms - Writing is slow and labored, and as it progresses, the letters get smaller and smaller - Postural movements are impaired Resting tremor: vibratory movements of the arms and hands that diminish somewhat when the individual makes purposeful movements - Accompanied by rigidity - joints appear stiff.

Cerebrovascular accidents: treatment - hemorrhagic stroke

Caused by high blood pressure: medication to reduce blood pressure Caused by weak or malformed blood vessels: brain surgery to seal off the faulty vessels to prevent another hemorrhage Caused by thrombus: dissolve or physically remove the blood clot. - Immediate treatment is not available: receive anticoagulant drugs to make the blood less likely to clot, reducing the likelihood of another stroke. If embolus broke away from a bacterial infection: antibiotics will be given to suppress the infection.

Tumors and seizures: seizures - petit mal seizures/absence seizures

Children are especially susceptible to seizure disorders - Many children do not have grand mal episodes Absence seizures/petit mal seizures: brief seizures - Generalized seizure - Symptom: child stops what they are doing and stares off into the distance for a few seconds, often blinking their eyes repeatedly. - Unresponsive, do not notice their attacks Absence seizures can occur several hundred times each day - can disrupt a child's performance in school - Many of children experiencing them are considered inattentive and unmotivated unless a seizure disorder is diagnosed.

Chronic traumatic encephalopathy (CTE)

Chronic traumatic encephalopathy (CTE): form of TBI. Results in neurodegeneration due to repeated head trauma. Received attention for its prevalence in athletes: NFL, everyday athletes, soccer players, boxers - Women soccer players: additional problems with hitting the ball with their head because they have less strong necks - Boxers: punch drunk, cannot function well. Pugilistic dementia Diagnosis of CTE is confirmed by postmortem examination of brain tissue Symptoms: mood and cognitive impairment appear years after the injury Reduced brain volume and enlarged ventricles - Corpus callosum, regions of the cortex, and the limbic system appear to be damaged - characteristic deficits in executive control and mood regulation that are associated with this disease

Traumatic brain injury: closed-head injuries

Closed-head injuries: projectile or a fall against a sharp object that fractures the skull, causing the brain to be wounded by the object or a piece of the broken skull. - Can cause severe injury or death - Brain is hit, it will smash against the direct location of impact, then recoil in the opposite direction and smash against the other side Coup: direct damage - brain hits the inside of the skull on the side that is impacted by the hit(s) Contrecoup: indirect damage - brain hits the inside of the skull on the side that is not directly impacted. The brain hits the side of the skull that is impacted but it then moves and hits the other side Can damage more than the cerebral cortex at the point of the coup and contrecoup - Bundles of axons can be torn and twisted, blood vessels can be ruptured, and cerebrospinal fluid can distort the walls of the ventricles. Traumatic brain injury can be followed several months later by seizures.

Degenerative disorders: Alzheimer's disease

Degenerative brain disorder of unknown origin. Causes progressive memory loss, motor deficits, and eventual death As you get older, you lose brain tissue which results in brain disfunction Form of dementia: loss of cognitive function. There are a number Amyloid plaque disorders: extracellular deposit containing dense core of β-amyloid protein surrounded by degenerating axons and dendrites and activated microglia and reactive astrocytes - Most common form is due to amyloid plaque - Before, you would be diagnosed with Alzheimers when you die when you see the plaque - Memory deficits (prospective memory, anomia, STM) - We can now diagnose Alzheimer patients when they are alive through brain scanning Neurofibrillary Tangles: associated with Pick's frontotemporal disease - Language, emotional and executive deficits

Degenerative disorders: amyotrophic lateral sclerosis

Degenerative disorder that attacks spinal cord and cranial nerve motor neurons Symptoms: spasticity (increased tension of muscles, causing stiff and awkward movements), exaggerated stretch reflexes, progressive weakness and muscular atrophy, and, finally, paralysis - Muscles that control eye movements are spared - Some cognitive abilities, such as executive function, working-memory, language and social cognition may also be affected Death usually occurs 5-10 years after the onset of the disease as a result of failure of respiratory muscles

Degenerative disorders: Huntington's disease

Disease affects the basal ganglia - caused by degeneration of the caudate nucleus and putamen Symptoms: uncontrollable movements, especially jerky limb movements. - Movements look like fragments of purposeful movements but occur involuntarily - Begins: person's thirties and forties but can sometimes begin in the early twenties. First signs of neural degeneration occur in the putamen, in a specific group of inhibitory neurons Confabulation: they make up excuses for their uncontrolled behaviour of movements Disease is progressive: has cognitive and emotional changes, and leads to death Death occurs within 10-15 years after the symptoms begin

Disorders of development: down syndrome

Down syndrome: congenital disorder that results in abnormal development of the brain, producing intellectual disability in varying degrees Caused by the presence of an extra 21 chromosome Syndrome is associated with the mother's age - Error in meiosis produces an ovum that has two 21 chromosomes. Likelihood increases in women over 35 When fertilization occurs, the addition of the father's twenty-first chromosome makes three, rather than two, twenty-first chromosomes. - Extra chromosome causes biochemical changes that impair normal brain development Similarities to Alzheimer's disease Intellectual disability; brain degeneration in adulthood.

Cerebrovascular accidents: treatment - medication

Drugs that dissolve blood clots - reestablish circulation to an ischemic brain region - Some success tPA: clot-dissolving drug after the onset of a stroke - Inhibits the materials accumulating in the blood vesicles so they cannot stick to one another - inhibits fibrogen disrupts clotting - Has toxic effects in the central nervous system - excitotoxic injury Desmoteplase: anticoagulant enzyme. Isolated from the saliva of vampire bats - No excitotoxic injury when injected directly into the brain - More of it, the better the results.

Degenerative disorders: Parkinson's disease - causes - genetic

Genetic: mutation of a particular gene on chromosome 4 will produce this disorder - Gene produces a protein known as α-synuclein - Mutation of a gene on chromosome 6 that produces a gene that has been named parkin

Degenerative disorders: Parkinson's disease - treatment - gene therapy

Genetically modified virus into the subthalamic nucleus delivered a gene for GAD - enzyme responsible for the biosynthesis of the major inhibitory neurotransmitter, GABA Production of GAD turned some of the excitatory, glutamate-producing neurons in the subthalamic nucleus into inhibitory, GABA- producing neurons Result: activity of the GPi decreased, the activity of the supplementary motor area increased, and the symptoms of the patients improved

Tumors and seizures: seizures - grand mal

Grand mal: most severe form of seizure - Generalized - Includes motor systems of the brain - convulsions Before having a grand mal seizure: person has warning symptoms - changes in mood, sudden jerks of muscular activity upon awakening. - A few seconds before the seizure occurs, the person may experience an aura Aura: caused by excitation of neurons surrounding a seizure focus. - Nature of an aura varies according to the location of the focus - structures in the temporal lobe are involved in the control of emotional behaviors, seizures originating from a focus there begin with feelings of fear and dread or euphoria

Cerebrovascular accidents: causes - hemorrhagic strokes

Hemorrhagic strokes: bleeding within the brain - malformed blood vessel or from one that has been weakened by high blood pressure. Blood that leaks out accumulates in the brain, putting pressure on the surrounding brain tissue and damaging it

Degenerative disorders: Huntington's disease - causes

Hereditary disorder, caused by a dominant gene on chromosome 4 - Defect: repeated sequence of bases (called CAG repeats) that code for the amino acid glutamine Huntingtin (Htt): protein produced by the repeated sequence. Repeated sequence makes it contain an elongated stretch of glutamine. - Plays a role in vesicular transport, release of neurotransmitter, and recycling of vesicular membrane - Plays an essential role in development. Abnormal Htt: misfolded and forms aggregations that accumulate in the nucleus - Mutation causes the disease through a toxic gain of function - abnormal Htt causes harm - Abnormal Htt may trigger apoptosis by impairing the function of the ubiquitin- protease system, which activates caspase, one of the enzymes involved in apoptosis Death of neurons in Huntington's disease is apoptosis (cell "suicide") - Live longer if they were given a caspase inhibitor - suppresses apoptosis

Degenerative disorders: amyotrophic lateral sclerosis - causes

Hereditary: 10% - Supraoxide dismutase 1 (SOD1): normally protects against free radicals - usually a good thing and it protects the mitochondria by getting rid of free radicals - Mutation causes a toxic gain of function that leads to protein misfolding and aggregation, impaired axonal transport, and mitochondrial dysfunction - Impairs glutamate reuptake into glial cells - increases extracellular levels of glutamate and causes excitotoxicity in motor neurons - mutant SOD1 can be transmitted from cell to cell - no evidence that the disease can be transmitted between individuals (Münch and Bertolotti, 2011). Sportaic: 90% - Abnormal RNA editing so AMPA receptors admit too much Ca++ Excitotoxicity from accumulated Ca++ in neurons: to much calcium in the cell which leads to swelling and the cell then dies

Cerebrovascular accidents: causes - excitotoxicity

Immediate cause of neuron death is the presence of excessive amounts of glutamate Damage produced by loss of blood flow to a region of the brain is an excitotoxic lesion - similar to those produced in a laboratory animal by the injection of an excitotoxic chemical

Traumatic brain injury: treatment

Immediate, primary treatments for TBI: - Reducing swelling and intracranial pressure - Ensuring adequate blood flow to the injured region Secondary to the immediate brain injury: treatments address symptoms - Mild cases of TBI: greatly increase a person's risk of sustaining symptoms that are not immediately obvious but manifests later Assess and treat long-term behavioural and cognitive changes

Degenerative disorders: Parkinson's disease - treatment - implants

Implanting electrodes in the STN or the GPi and attaching a device that permits the patient to electrically stimulate the brain through the electrodes Deep brain stimulation (DBS) of the subthalamic nucleus: effective as brain lesions in suppressing tremors and has fewer adverse side effects - May have an effects on the affective and cognitive symptoms of Parkinson's disease such as depression and dementia

Disorders of development: inherited metabolic disorders - galactosemia

Inherited metabolic disorder in which galactose (milk sugar) cannot easily be metabolised - Inability to metabolise galactose in milk Sugar in milk that cannot be metabolises Treatment: changing their diets can help these individuals

Degenerative disorders: Parkinson's disease - causes

Involves the basal ganglia disrupts learned movements - Super sensitive: the basal ganglia is more sensitive to dopamine because it is getting less and less throughout the progression of the disorder Dominant mutation that involves faulty gene that produces protein with toxic effects You may not see symptoms over many years because the basal ganglia becomes more sensitive to the small amount of dopamine but then there is no dopamine so regardless of how sensitive they are, it creates the symptoms Almost complete loss of dopamine projection

Cerebrovascular accidents: causes - ischemic strokes

Ischemic strokes: block a blood vessel and obstruct the flow of blood - Ischemia: loss of blood flow to a region - Caused: thrombi or emboli

Degenerative disorders

Many disease processes cause degeneration of the cells of the brain. - Some of these conditions injure particular kinds of cells Prion infection: 1. Transmissible spongiform encephalopathies Motor behavior 1. Parkinson's disease 2. Huntington's disease 3. Amyotrophic lateral sclerosis 4, Multiple sclerosis Cognition 1. Alzheimer's disease 2. Korsakoff's syndrome

Cerebrovascular accidents: treatment - surgery

Medical devices: both are inserted into a cerebral blood vessel and extended until they reach the obstruction 1. Corkscrew: grabbing the obstruction, pull clot out 2. Suction: tip of the device touches the obstruction, a vacuum is applied, and the surgeon pulls out the clot - Suction is more likely to produce clinical improvement and less likely to cause intracerebral bleeding Disadvantage: some clots are difficult to reach, and attempts at mechanical removal can further damage the blood vessels Stent: placement in a narrowed carotid artery - Arterial stent: implantable device made of mesh that is used to expand and hold open a partially occluded artery - Use of carotid stents is associated with an increased number of future strokes and the death rate following implantation is higher

Disorders of development: inherited metabolic disorders - pyridoxine dependency

Metabolic disorder in which an infant requires larger-than-normal amounts of pyridoxine (vitamin B6) to avoid neurological symptoms Symptoms: damage to cerebral white matter, to the thalamus, and to the cerebellum Treatment: large doses of vitamin B6

Cerebrovascular accidents: treatment - after a stroke occured - mirror neurons

Mirror neurons in the parietal lobe and ventral premotor cortex become active when a person performs an action or sees someone else performing it. Therapy: combined repetitive practice of hand and arm movements used in daily life with the watching of videos of actors performing the same movements Results: patients' motor functions showed long-term improvement - fMRI: increased activity in brain regions involved in movement

Degenerative disorders: Alzheimer's disease - treatment

Most of them are unsuccessful Cognitive reserve: if you have a good intellectual live, you can stave off getting the disease - Animal model in mice: reproduce the symptoms - Some animals just progressed into the disease - Other animals were trained on maze like tasks. Those who were trained were less likely to get get alzheimer's disease Acetylcholinesterase inhibitors NMDA receptor antagonist Immunological: research is promising. Get your normal immune system and get them to get rid of the amyloid plaques naturally

Degenerative disorders: Parkinson's disease - causes - genetic - parkin

Mutation of a gene on chromosome 6 that produces a gene that has been named parkin - Genetic disorder caused by recessive gene that fails to produce protein that is necessary for good health Mutation causes a loss of function Normal parkin: role in transferring defective or misfolded proteins to the proteasomes (organelles that destroy proteins) 1. Parkin assists in the tagging of abnormal or misfolded proteins with numerous molecules of ubiquitin (small, compact globular protein) 2. Ubiquitination (as this process is called) targets the abnormal proteins for destruction by the proteasomes - break them down into their constituent amino acids Mutation: high levels of defective protein to accumulate in dopaminergic neurons and ultimately damage them - Defective parkin fails to ubiquinate abnormal proteins, and they accumulate in the cell, eventually killing it - If α-synuclein protein is defective because of a mutation, Parkin is unable to tag it with ubiquitin, and defective α-synuclein accumulates in the cell.

Disorders of development: inherited metabolic disorders -Tay-Sachs disease

Occurs mainly in children of Eastern European Jewish descent Causes brain to swell and damage itself against the inside of the skull and against the folds of the dura mater that encase it Neurological symptoms begin by four months of age and include an exaggerated startle response to sounds, listlessness, irritability, spasticity, seizures, dementia, and finally death. Leads to death Is a metabolic "storage" disorders: - Cells contain sacs of material encased in membrane, called lysosomes. These sacs are the waste-removal system; they contain enzymes that break down waste substances that cells produce in the course of their normal activities. The broken-down waste products are then recycled (used by the cells again) or excreted Metabolic storage disorders: genetic errors of metabolism. At least one vital enzyme is missing. Particular kinds of waste products cannot be destroyed, so they accumulate in the lysosomes. The lysosomes get larger and larger, the cells get larger and larger, and eventually the brain begins to swell and become damaged. Treatment: genetic engineering - Develop genetically modified viruses that will insert into infants' cells the genetic information needed to produce the enzymes that the cells lack, leaving the rest of the cells' functions intact.

Tumors and seizures: seizures - partial, generalized, simple and complex

Partial seizures: definite focus - usually a scarred region caused by an old injury or a developmental abnormality - Neurons involved in the seizure are restricted to a small part of the brain Simple and complex partial seizures: - Simple partial seizures: cause changes in consciousness but do not cause loss of consciousness. - Complex partial seizures: particular location and severity, they lead to loss of consciousness Generalized seizures: widespread, involving most of the brain - Sometimes they grow from a focus - sometimes their origin is not discovered - If they have an area of focus - where the activity begins. The tissue around that area will be excited and area around it will get over excited as well. Neurons in these areas have connections to other parts of the brain, and through the corpus callosum, the other side of the brain can be activated as well

Tumors and seizures: seizures - partial seizures

Partial seizures: small portions of the brain Symptoms: sensory changes, motor activity, or both Begins in or near the motor cortex: jerking movements that begin in one place and spread throughout the body

Cerebrovascular accidents: treatment - after a stroke occured - constraint-induced movement therapy

Patients with strokes that impaired their ability to use one arm and hand Put the unaffected arm in a sling for 14 days and gave the patients training sessions - patients were forced to use the affected arm Placebo group: cognitive, relaxation, and physical fitness exercises for the same amount of time Results: long-term improvement in the patients' ability to use the affected arm - Constraint-induced movement therapy: changes in the connections of the primary motor cortex.

Traumatic brain injury: penetrating brain injuires

Penetrating brain injuries/open-head injuries: damage to the portion of the brain that is injured by the object or the bone - Damage to blood vessels can deprive parts of the brain of their normal blood supply, and the accumulation of blood within the brain can cause further damage by exerting pressure within the brain

Disorders of development: inherited metabolic disorders - phenylketonuria (PKU)

Phenylketonuria (PKU): is the most common Cause: inherited lack of an enzyme that converts phenylalanine (an amino acid) into tyrosine (another amino acid) - Excessive amounts of phenylalanine in the blood interfere with the myelinization of neurons in the central nervous system. Much of the myelinization of the cerebral hemispheres takes place after birth. When an infant born with PKU receives foods containing phenylalanine, the amino acid accumulates, and the brain fails to develop typically Symptoms: severe intellectual disability Treatment: putting the infant on a low-phenylalanine diet. Diet keeps the blood level of phenylalanine low, and myelinization of the central nervous system takes place normally.

Degenerative disorders: transmissible spongiform encephalopathies - prions - role

PrPc: not essential for the life of a cell Normal prion protein: role in neural development and differentiation in fetuses and neurogenesis in adults. - Prionlike mechanism: role in the establishment and maintenance of long-term memories. Long-term memories can last for decades, and prion proteins might maintain synaptic changes for long periods of time. Cells can commit suicide - apoptosis. Apoptosis can be triggered externally, by a chemical signal telling the cell that it is no longer needed (for example, during development), or internally - Accumulation of misfolded, abnormal proteins provides such a signal. Caspases: killer enzymes. Apoptosis produces these. - Inactivation of caspase-12, the enzyme that appears to be responsible for the death of neurons infected with PrPSc, may provide a treatment that could arrest the progress of transmissible spongiform encephalopathies

Degenerative disorders: Parkinson's disease - treatment - lesions

Principal output of the basal ganglia: internal division of the globus pallidus (GPi). This output, which is directed through the subthalamic nucleus (STN) to the motor cortex, is inhibitory - Decrease in the activity of the dopaminergic input to the caudate nucleus and putamen causes an increase in the activity of the GPi. Damage to the GPi might be expected to relieve the symptoms of Parkinson's disease Pallidotomies: surgical destruction of the internal division of the globus pallidus. Reduces rigidity and enhances ability to move. Surgery made the patient's symptoms worse and sometimes resulted in partial blindness. Find location of the GPi and inserted an electrode. Then pass radiofrequency current to heat and destroy the brain tissue. The results of this procedure were promising Subthalamic nucleus has an excitatory effect on the GPi; therefore, damage to the subthalamic nucleus decreases the activity of this region and removes some of the inhibition on motor output. This surgery brings depressed motor activity back to normal

Degenerative disorders: transmissible spongiform encephalopathies - prions

Prions: simple proteins that cause TSEs - Primarily found in the membrane of neurons - play a role in synaptic function and in preservation of the myelin sheath Prion proteins are resistant to proteolytic enzymes (enzymes that destroy proteins) - Resistant to levels of heat that denature normal proteins Sequence of amino acids of normal prion protein (PrPc) and infectious prion (PrPSc) are identical - Only difference between PrPc and PrPSc is the way the protein is folded Introduction of misfolded PrPSc: causes normal PrPc to become misfolded too, and the process of this transformation ultimately kills them They can be genetic or sporadic and they can be transmitted to others - Most cases of TSEs are sporadic: occur in people without a family history of prion protein disease

Cerebrovascular accidents: treatment - risk factors

Risk factors: high blood pressure, cigarette smoking, diabetes, and high blood levels of cholesterol Atherosclerosis: linings of arteries develop a layer of plaque. - Precursor to heart attacks (myocardial infarction) and ischemic stroke, caused by clots that form around atherosclerotic plaques in cerebral and cardiac blood vessels.

Tumors and seizures: seizures

Seizure: period of sudden, excessive activity of cerebral neurons - If neurons that make up the motor system are involved, a seizure can cause a convulsion (uncontrollable activity of the muscles) - Not all seizures cause convulsions - most do not A single seizure can occur (result of an injury or tumor) or a person may experience many seizures during a lifetime Seizure disorder: condition that has many causes

Tumors and seizures: seizures - grand mal - status epilepticus

Status epilepticus: worse case of generalised seizures - One grand mal seizures after another - life threatening Patient undergoes series of seizures without regaining consciousness Symptoms: - Vegetative conditions - stop breathing - People do recover from them after a period of time - Over time they can get worse and longer Damage: excessive release of glutamate during seizure - Excessive activity will cause nerve damage Excitotoxic lesion: creating over activity on purpose - Glutamate: normally acts on excitatory receptors. You can experimentally inject glutamate or glutamate type substances into the brain and it causes excessive activity of neurons which kills the cells. - Advantage: it will only be effective where the injection is placed in the cell bodies, not the axons. It will be more specific.

Degenerative disorders: Parkinson's disease - treatment - optogenetic methods

Stimulate or inhibit specific types of neurons in specific locations of the brain with light- sensitive proteins Activation of the direct pathway inhibits the GPi and activation of the indirect pathway excites the GPi - Indirect pathway: excites the GPi, causes displays of motor symptoms - Direct pathway: stimulated this pathway, which inhibits the GPi, the parkinsonian symptoms disappeared

Cerebrovascular accidents

Strokes: impairments in perception, emotional recognition and expression, memory, and language Strokes in the US: 750,000 per year - Likelihood of having a stroke is related to age - probability 2x each decade after 45. Reaches 1-2% per year by 75 Two major types of strokes: hemorrhagic and ischemic

Traumatic brain injury: treatment - drugs

TBI results in increased levels of adenosine and glutamate in the injured brain tissue - Increased glutamate converts the adenosine from its normal role as an anti-inflammatory agent to an agent that promotes inflammation - Drug that inhibits the release of glutamate can prevent this switch in the role of extracellular adenosine

Disorders of development: toxic chemicals - teratogen

Teratogen: chemical or toxin that results in abnormal development of an embryo Rubella (German measles): if a women contracts it early in pregnancy, the toxic chemicals released by the virus interfere with the chemical signals that control typical development of the brain

Degenerative disorders: multiple sclerosis - treatment

There really is no effective treatment Stop attacking the normal myelin

Degenerative disorders: amyotrophic lateral sclerosis - treatment

They don't seem to improve things that much. No good viable treatments for ALS

Cerebrovascular accidents: causes - ischemic strokes - thrombi or emboli

Thrombus: blood clot that forms in blood vessels - common in places where walls are already damaged - Thrombi become so large that blood cannot flow through the vessel, causing a stroke People who are susceptible to the formation of thrombi are advised to take a drug such as aspirin - helps prevent clot formation An embolus: piece of material that forms in one part of the vascular system, breaks off, and is carried through the bloodstream until it reaches an artery too small to pass through - It lodges, damming the flow of blood through the rest of the vascular tree - Emboli: variety of materials - bacterial debris from an infection in the lining of the heart or pieces broken off from a blood clot

Tumors and seizures: seizures - grand mal - phases

Tonic phase: beginning of a grand mal seizure - All of muscles contract forcefully - arms are rigidly outstretched, and the person may make an involuntary cry as the tense muscles force air out of the lungs (patient is unconscious.) Clonic phase: begins after person holds a rigid posture for fifteen seconds - Muscles begin trembling, then start jerking convulsively— quickly at first, then more and more slowly - Eyes roll, the person's facial muscles contract, and the tongue may be bitten - Activity of the autonomic nervous system: sweating and salivation. - After a short period, muscles relax; then regular breathing begins again Person may fall into an unresponsive sleep (can last for minutes) - Person may awaken briefly but usually falls back into an exhausted sleep that may last for several hours

Degenerative disorders: Parkinson's disease - treatment - transplantation of fetal tissue

Transplantation of fetal tissue: reestablish the secretion of dopamine in the neostriatum. - No longer recommended - Motor disfunction that don't result in long-term improvements - Most of the transplants are ineffective

Degenerative disorders: Huntington's disease - treatment

Treatment: there is no treatment for Huntington's disease Block transcription of the abnormal Huntington protein No effective treatments are known Intrabodies block Htt gene Small interfering RNA (siRNA) blocks protein transcription

Tumors and seizures: tumors - different types and metastasizing

Tumor: mass of cells with uncontrolled growth, that serves no useful function - Malignant: cancerous. Often metastases - Benign: harmless, most common Distinction of malignancy and benignancy: tumor is encapsulated - distinct border between the mass of tumor cells and the surrounding tissue - With border: benign. Can be cut out, and it will not regrow. - No border: growth infiltrates surrounding tissue - no border between the tumor and healthy tissue. Some cells will be missed when removed and can regrow Metastasizing tumor: shed cells --> travel by bloodstream --> lodge in capillaries --> growth of new tumors in different locations

Tumors and seizures: tumors - compression and infiltration

Tumors damage brain tissue by two means: compression and infiltration - Benign tumors: compression - Malignant tumors: cause compression and infiltration Compression: Tumors occupy space and push against the brain. Compression can directly or indirectly destroy brain tissue. Indirectly - blocks the flow of cerebrospinal fluid and causes hydrocephalus Malignant tumor grows - invades surrounding region and destroys cells in its path.

Tumors and seizures: tumors - causes

Tumors do not arise from nerve cells. They arise from cells in the brain or from metastases originating in the body Most serious tumors: are metastases and the gliomas (glial cells) - very malignant and fast growing

Cerebrovascular accidents: treatment - after a stroke occured - brain-computer interface

When patients are unable to perform useful limb movements Brain-computer interface: permit the patient to control electronic and mechanical devices to perform useful actions Implanted arrays of microelectrodes directly into the patient's motor cortex and have applied surface electrodes to measure changes in EEG activity transmitted through the skull and scalp These devices permit patients to move prosthetic hands, perform actions with multi-jointed robotic arms, move the cursor of a computer display, and operate a computer

Degenerative disorders: Parkinson's disease - treatment - drug treatment

l-DOPA: precursor of dopamine - Increased level of l-DOPA in the brain causes a patient's remaining dopaminergic neurons to produce and secrete more dopamine and, for a time, alleviates the symptoms of the disease - Eventually the number of dopaminergic neurons declines to such a low level that the symptoms become worse Deprenyl: often given in conjunction with l-DOPA. Inhibits the activity of the enzyme MAO-B - Inhibits MAO-B (normally breaks down dopamine) prevent MAO-B degradation of dopamine - Benefits: reduction in symptoms - Drugs do not appear to slow the degeneration of dopaminergic neurons

Degenerative disorders: Parkinson's disease - causes - genetic - α-synuclein

α-synuclein: normally found in the presynaptic terminals. Involved in synaptic transmission in dopaminergic neurons - Mutation produces a toxic gain of function - produces a protein that results in effects that are toxic to the cell Abnormal α-synuclein: misfolded and forms aggregations of dopaminergic neurons - Dense core of Lewy bodies consists primarily of these aggregations, neurofilaments, and synaptic vesicle proteins. 1. You have a gene that creates the α-synuclein (normally does a lot of good things for the body) and when it succeeds its useful life it needs to be destroyed and recycles 2. The body needs to identify the bad α-synuclein which is then identified by Parkin 3. Bad α-synuclein is then tagged by the ubiquitin 4. Tag is used by the proteasome which destroys the bad tissue (normall found in the synaptic vesicles). It breaks it down to its regular components