Sem 2 L1- Brain Damage And Neurodegeneration Flashcards

Question

Who does Parkinson’s disease affect?

Answer 1

0.5% of the population (1.2% of the elderly population), 2.5x more common in men Parkinson’s Disease is an idiopathic disease - each case has its own origins (no single cause) It is a neurodegenerative disease, no cure, some treatment options available that reduce the symptoms

Answer 2

Involuntary tremulous motion with lessened muscular power. in parts not in action and even when supported, with a propensity to bend the trunk forward, and to pass from walking to a running pace, the senses and intellects being uninjured

Answer 3

Paucity of spontaneous movement - insufficiency of movement Bradykinesia - very slow movements Akinesia - no movements Increased muscle tone - rigidity Resting tremor - @4-5hz - 'pill rolling' Shuffling gait and flexed posture, impaired balance Mask-like expression - bc it affects muscles in face with insufficiency of movement and slow movements, no movements and rigidity - there is an initiation of (selection of) + movement is impaired , but certain cues / contexts can help eg the bike riding

Answer 4

A deficiency (loss) from neurons that release a single neurotransmitter or a loss of a single neurotransmitter eg dopamine lack of dopamine in a particular pathway of the brain - the nigrostriatal dopamine pathway found within the basal ganglia. so that dopamine pathway is broken down 80% of brains dopamine is in the basal gangla parkinsons disease sufferers are deficient in dopamine in the striatum when we lose that release of dopamine we end up in this stuck state , cant initiate movement

Answer 5

sits deep within the brain and inhibits motor output. stops motor system from doing 50 things at once, allowing your motor system to be controlled In parkinsons disease this inhibition doesnt get switched off at all so motor system is stuck bc the burst of dopamine allows for this basal ganglia to allow the inhibition to be reduced to allow ur motor system to go. but in pd you lose the burst of dopamine so basal ganglia over inhibits. thats why you need additional triggers to get over the inhibition.

Answer 6

The motor system to get you to do your movements

Answer 7

Surgical intervention - -Lesion the relevant part of the BG (the globus pallidus) and symptoms reduce or disappear/ (but not something humans would like) only in severe cases -Electrical stimulation of basal ganglia (Deep Brain Stimulation) - an electrode is planted into some structures & reduce excessive inhibition or levels of activity. Target sites as lesion but w electrical current tuned to shut them down (inhibit output) - reversible, controllable, adjustable Replace lost DA (dopamine) cells - initial indications of success for fetal/stem cell transplantation have not been underpinned in larger, longer term trials, at least in terms of balancing risks Replace the lost dopamine -

Answer 8

give dopamine BUT BUT just giving dopamine doesnt allow the dopamine to be replaced where exactly it is lost. and dopamine doesnt cross the Blood brain barrier (wont cross from the blood vessels into the brain tissues) SO GIVE THIS DRUG Levo Dopa (dopamine precursor) - which crosses over the blood brain barrier - gets taken up by the neurons which make dopamine to help them make even more dopamine so its v effective in reduction of symptoms of parkinsons disease more drugs Apomorphine - dopamine agonist - mimics effects of dopamine Deprenyl (monamine {dopamine/serotonin} agonist Cannabis? A dopamine agonist, seems effective in some cases but overall not backed up by larger scale studies (at least compared to the above)

Answer 9

10% over 65 yrs old 35% over 85 years old range of dementias memory loss selective decline in memory deficits in attention and personality changes immediate stages - confusion, anxiety, irritability final stages - swallowing and bladder control

Answer 10

Mini-Mental State Examination (MMSE) Cognitive test battery can look at scores for individual compared to where you might expect them to be for their age various predictors for that eg latest stage of education they got to Imaging - eg amyloid protein in the brain but some people can have a lot of amyloid and have no symptoms of dementia but some ppl can have little amyloid and have symptoms of dementia (AZ) shrinkage of brain and enlagement of fluid filled surfaces postmortem tissue after death but hard to pin down

Answer 11

Shrinkage of brain and enlargement of fluid filled spaces accumulation of protein called amyloid (normally means starch but its a protein) Amyloid is a protein we have - part of normal cellular function. but in AZ a chunk of it gets broken off and accumulates of sticky lumps of amyloid around neurons. (lumps of amyloid beta/beta amyloid which is part of the amyloid protein) their existence around neurons compromises the env neurons are in and this can be toxic to them and lead to degeneration. so this is how amyloid causes az disease.

Answer 12

Normally the amyloid sticks itself and sits within the walls of cells in the brain. its functions involve cellular development and communication within cells.

Answer 13

Amyloid proteins can be snipped off by enzymes, breaking off the beta amyloid chunks. In Alzheimers disease the beta-amyloid chunks stick together (to make/form a beta-amyloid plaque) Function is not fully understood. But the amyloid protein can be snipped off and processed in two different pathways.

Answer 14

The amyloid protein can be snipped and processed by a good one or bad one. The amyloid protein can be snipped, then broken down and recycled and the brain having enzymes which breaks down proteins, recycles and rebuilds them it just a normal part of the brain which happens all the time. IN AZ disease what we think contributes to it is that the amyloid protein is broken up in the wrong place, which leads to the beta amyloid bits being chopped out and stuck to each other. dont know how and why that happens but that leads to an accumulation of this amyloid protein which impairs the function of cells.

Answer 15

Found on chromosome 21 - down syndrome is particularly associated with the development of az disease. bc the amyloid precursor protein (APP) is on chromosome 21 and there is an additional representation of that chromosome in az disease. that's why there tends to be an increased likelihood of that. 150% of normal APP levels. Develop AD pathology by 40 years old Genetic forms of AD appear to have an early onset They are usually (additional) mutations in the APP gene

Answer 16

Proteins come about through this gene. There are different flavours of this - eg - E2, E3, E4. Different versions of that can lead you to be more or less likely to develop alzheimers disease. So having a particular protein such as the E4 protein you might be MORE likely to develop Alzheimers disease. Having the apolipoprotein E2 may decrease your likelihood of developing AZD. the difference in protein is just the shape of the protein. In the periphery it is involved in transport of cholesterol. Ties in w how high cholesterol and cardiovascular disease being a cardio risk factor being associated w ^ risk of AZ D.

Answer 17

An alternate form of a gene - w ehave many of these eg determining hair colour

Answer 18

Tau is a protein. Tau normally helps form microtubules within our neurons which can support the structure of the neuron. They are part of the cytoskeleton - keeping a cells shape. Can be important for the movement of substances up and down neurons.

Answer 19

Tau gets into a muddle and gets tangled up. You get clumps of Tau.

Answer 20

Microtubule Associated Proteins (MAPs) Tau is a MAP Problematic protein that accumulates in sticky lumps and impairs the function of cells and leads to a loss of neurons

Answer 21

Animal models where genetic modification leads to excessive APP, TAU, or copies of genes coding for the apoE E4 allele helping to clear?? amyloid There are "double" or "triple" transgenics that include genetic encoding for 2 or 3 of these features BUT are these mice actually getting AD?? (no, theyre replicating components of human AZD.

Answer 22

Elusive ppl have tried to get the immune system to recognise amyloid shouldnt be there and to attack it and break it down and remove it there are some evidence that we can do it. it doesn't cure the disease but reduces the progression of alzheimers disease.

Answer 23

Loss of neurons that produce/ release the neurotransmitter acetylcholine

Answer 24

Acetylcholine - important for normal cognitive function, especially memory formation. helps to bind the activity of neurons together to form memories. for various reasons, these cholinergic neurons that release acetylcholine seem to be particularly vulnerable to effects of alzheimers disease in the brain so they die off, so we lose acetylcholine so the idea of treatment is to reduce the impact of this and increase and restore the amount of acetylcholine.

Answer 25

Reduce the impact of this and increase and restore the amount of acetylcholine. An enzyme in the brain (Cholinesterase) (AchE) normally breaks down acetylcholine. Inhibiting Cholinesterase, allows for the slowing down of the breaking down of the neurotransmitter acetylcholine, allowing for the nt to hang around for longer making up for ht fact that there is not as much there as there was in the first place. so u prevent breakdown, preventing acetylcholine from continuing to act on the neurons (normally a good thing) Inhibit AchE (Cholinesterase), increasing (prolonging) the effect of acetylcholine on the neurons. remains at the synapses in the form of drugs

Answer 26

Cholinesterase inhibitors Include donepezil hydrochloride (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) Donepezil hydrochloride helps to restore blood flow to the brain as well (not just effect memory function). bc we think blood flow is important.