OTH 509: Final Exam

OTH 509: Final Exam Neuropathology of Alzheimer's Disease Beta amyloid plaques and tau-based neurofibrillary tangles (NFTs) Over the past several years tauopathy (NFTs) have been found to be most robust predictors of clinical syndrome Additionally, recent research has also found problematic inflammation and immune-related issues in AD Typically pathology starts in medial temporal lobe and progresses laterally, posteriorly, and anteriorly Retrograde amnesia (RA) loss of memories from our past Anterograde amnesia (AA) an inability to form new memories Alzheimer's disease (AD) ELEVATED levels of depression & anxiety behavioral dysregulation inability to store new information has insidious onset/slow build up over time Risk factors for Alzheimers older age female lower education APOE-4 status history of TBI History of mental illness history of ETOH abuse T or F: Alzheimer's is the most common form of dementia. True Typical age of onset of Alzheimer's 70-75 years old Risk factors for Lewi-body dementia age men family history Lewi-body dementia age of onset mid-50s to late 60s Lewy Body Dementia (LBD) presents as fluctuating cognition with pronounced variation in attention and alertness recurrent visual hallucinations REM sleep behavior disorder More spontaneous cardinal features of Parkinsonism (bradykinesia, rest tremor, rigidity) What are the 3 types of frontotemporal dementia? behavioral variant semantic dementia primary progressive aphasia Frontotemporal Dementia: BEHAVIORAL VARIANT could present as socially inappropriate behavior loss of manners impulsive apathy/interia diminished social interest or response to people's feelings simple repetitive movements complex compulsive behaviors altered food preferences binge eating or consumption of inedible objects deficits in executive tasks (including episodic memory and visuospatial skills) Frontotemporal Dementia: SEMANTIC DEMENTIA onset and gradual progression language disorder characterized by progresssive empty spontaneous speech loss of word meaning manifested by impaired naming or comprehension or semantic paraphasias loss of sympathy and empathy parsimony absent or late primitive reflexes akinesia rigidity tremors Prevalence and risk factors for frontotemporal dementia: 5-9% of all diagnosed dementia cases Age gender (MF) history of psychiatric diagnosis family history of FTLD Describe treatment principles for management of dementia and name common drugs Galantamine, rivastigmine, and donepezil are cholinesterase inhibitors that are prescribed for mild to moderate Alzheimer's symptoms. These drugs may help reduce or control some cognitive and behavioral symptoms. T or F: Dementia has no cure, so best of course of action is to mange symptoms (agitation and paranoia resulting from dementia can be treated with medication) True What do SNARE proteins do? assist in the specific binding of the vesicle membrane to the cell membrane, SPECIFICALLY v-SNAREs on the vesicle and t-SNAREs on the cell membrane What is SNARE proteins role at the synapse? Botulism ( a type of bacteria) destroy certain of the SNARE proteins in the presynaptic terminals, critical for neurotransmitter release Describe Metatrophic Receptors: G mediated receptors (SLOWER) Neurotransmitter molecules bind to receptor proteins embedded in the postsynaptic membrane Receptor proteins activate small proteins, called G proteins which move along the intracellular face of the post synaptic membrane Activated G proteins activate "effector proteins" These either activate G protein gated ion channels Or they can be enzymes that produce "second messenger Describe Ionotrophic Receptors: Ligand or Transmitter Gated Ion Channels (FASTER) Membrane spanning proteins that consist of 4-5 sub-units to form a pore between them; pore is usually closed in absence of neurotransmitter When neurotransmitter is present, the conformational change causes pore to open Ligand gated ion channels consist of proteins that function like a gate The gate of these channels opens in response to a chemical transmitter binding to the receptor surface; If neurotransmitter is not bound to the receptor of a ligand-gated channel, the gate is closed and no ions pass through What neurotransmitter is associated with neuronal death after CNS injury? Glutamate accumulation leads to overstimulation of postsynaptic glutamate receptors with intracellular Ca2+ overload and neuronal cell death How are neurotransmitters synthesized? Arrival of the action potential in the axon terminal causes voltage gated calcium channels in the active zone to open and an influx of calcium to occur The resulting increase in Ca+2 is the signal that causes neurotransmitter to be released from the vesicles by a process known as exocytosis SNARE proteins assist in the specific binding of the vesicle membrane to the cell membrane Binding of neurotransmitter to the receptor is like inserting a key in a lock Describe how neurotransmitters are reconstituted into vesicles (SHORT run): Kiss and run (fast): a type of synaptic vesicle release where the vesicle opens and closes transiently. In this form of exocytosis, the vesicle docks and transiently fuses at the presynaptic membrane and releases its neurotransmitters across the synapse, after which the vesicle can then be reused Describe how neurotransmitter are reconstituted into vesicles (LONG run): G protein mediated receptors (metabotropic) mechanism of receptor activation (SLOWER): have to have an intermediary called the G proteins, before you get the post synaptic change in potential Know how receptor agonists/antagonists and enzymes work pharmacologically to alter amounts of neurotransmitter to treat various diseases Agonist to these substances will mimic the action of the neurotransmitter The antagonist will block movement Ex. Acetylcholine's agonist is nicotine, so when nicotine is present it will mimic the action of Ach, but if Curare is present (Ach antagonist), it will block the normal effects of Ach Define dependence: acquired tolerance to a drug and you will have withdrawal if removed