NeuroDiseasesDrugs_Lab10_LimbicSleepDementia.txt

genetic condition. Causes failure to enter deep sleep. Can lead to death

sleep related disorder that can occur during arousals from sleep

promotes awake state by increasing monoamine transmission (serotonin - raphe nuclei and NE - locus of coerulus to the thalamus)

promotes awake state by increasing monoamine transmission (serotonin - raphe nuclei and NE - locus of coerulus to the thalamus). Also Histamine and Orexin mechanism

promotes awake state via adenosine receptor antagonist

promotes sleep state by increasing GABA output from VLPO (hypothalamus) to inhibit cholinergic (pons-midbrain junction), histamine (TMN) and monoamines (raphe nuclei and locus of coerulus).

promotes sleep by blocking histamine transmission (TMN)

Bilateral medial temporal lesion (amygdala). Amnesia (when bilateral hippocampus affected), decreased anxiety towards fear (amygdala), hypersexuality (amygdala-hypothalamic connection), visual agnosia (damage to inferior temporal lobe "what" pathway), hyperorality. Can be caused by herpes encephalopathy, trauma or hypoxia.

Calcification of the anterior-medial temporal lobe. Loss of ability to percieve fear, recognize fear, or a deficit in experiencing fear.

Anterograde amnesia (retrograde to a lesser extent) observed in chronic alcoholics. Vit B1 deficiency and degeneration in mammillary bodies and medial thalamus. The two are different stages of the same psychosis. Wernicke's encephalopathy is the acute and reversible characterized by the triad (opthalmoplegia, ataxia, confusion). Treatment with thiamine can prevent progression to Korsakoff level. Korsakoff's amnesia is the chronic and irreversible phase with essential deficit of being unable to form new memories and tendency to confabulate (make stuff up). Gait and oculomotor symptoms remain.

Progressive and exaggerated neurodegeneration of limbic system effecting the elderly. Irreversible dementia. Definitive diagnosis can only be made after histo analysis to find Beta amyloid plaques (extracellular) and tau tangles (intracellular) are present in histo stains. Specifically Entorhinal Cortex (medial temporal lobe) or basal forebrain is affected.

Hippocampal formation important for learning and memory formation; Associate Cortex <---> Entorhinal Cortex --perforant pathway--> Dentate Gyrus --mossy fiber--> CA3 --schaffer collateral--> CA1 ----> Subiculum ----> Entorhinal COrtex (back)

Tests learning in Hippocampus. Hippocampal lesion results in rodent unable to find hidden platform even after numerous days of practice.

Phineas Gage personality change after lesion here. Left lesion causes depression. Right lesion causes mania.

Voluntary Motor or Autonomic emotional feedback (Amygdala). Cortex ++++> Striatum ----> Pallidum ----> Thalamus ++++> Cortex (feedback)

Familial version is rare and due to an inherited mutation in PS1, PS2, or APP genes. Highly penetrant so for sure will get Alzheimers. Sporadic version is more common and due to a Single Nucleotide Mutation (point mutation) in ApoE (apoE4 mut causes Cys---> Arg 112). This is of low penetrance so at a higher risk for Alzheimers but not neccessarily doom to get the disease if you have apoE4 mutation.

Treatment for Alzheimers disease. Acetylcholinesterase inhibitor (increases levels of AcH at synaptic junction).

Treats Alzheimers via glutamatergic modulator on NMDA receptor. Remember AD is primarily a degeneration of glutamatergic synapses and LTP mechanisms.

In general a malfunction of dopamine pathway. Positive symptoms (VTA-mesolimbic projections) are the presence of abnormal behavior, delusions, and hallucinationsc caused by hyperdopamine transmission to D2 receptors mostly. Treat with antipsychotic drugs (APD) which are D2 receptor antagonists. Negative symptoms (VTA-mesocortical projection) are absence of normal social behavior such as apathy, avolition, anhedonia, alogia, and inappropriate affect caused by low dopamine activity. These chronic symptoms do not respond to APD and are difficult to treat.

An extrapyramidal (nigrostriatal) side affect of APD treatment of schizophrenia. Resting tremor, rigidity, difficulty initiating movement. Treat with anticholinergic drugs.

An extrapyramidal (nigrostriatal) side affect of APD treatment of schizophrenia and L-DOPA treatment of Parkinson's disease. Characterized by uncontrollable movement of the face, mouth and tongue. No effective treatment for Tardive.

Atypical APD to treat Schizophrenia. Binds non-dopaminergic receptors (5HT2A, H1, A1). Works for positive and negative symptoms. Less side affects than typical APD

Alzheimers and vascular dementia

Vitamine B1 deficiency, alcoholism, depression,and thyroid disease

Typical APD to treat only postitive symptoms of Schizophrenia. Binds D2 dopamine receptors only. Has side affects like Tardive dyskinesia and parkinsonian syndrome.

Bitemporal hemianopsia (tunnel vision) due to compression of optic chiasm and menstrual problems due to endocrine disorder.

Lesion/tumor in Orbitofrontal cortex. Compresses optic nerve and olfactory tracts. Visual loss in one eye with papilledema in the other, increased intracranial pressure, apathy, anosmia.

Diabetes symptoms from distruption of ADH secreting neurons in the paraventricular and supraoptic nuclei of the hypothalamus. Neurons synapse on the posterior pituitary which can also be damaged during this surgery.