Neurodegenerative disorders

Question 1

Name 4 symptoms of Parkison’s disease

Answer 1

1. Muscle rigidity
2. Akinesia (inability to initiate movement)
3. Bradykinesia (slowness)
4. Resting tremor

Question 2

What are the physical causes of Parkinson’s disease?

Answer 2

• Loss of dopamine neurons from the midbrain
• Loss of substantia nigra pars compacta, although symptoms only appear after 70% is lost with more from putamen than caudate nucleus
• Presence of Lewy bodies on neuron cytoplams

Question 3

What is the main pathway affected by Parkinson’s disease?

Answer 3

Less activity in the caudate nucleus causes less inhibition of the Globus pallidus and hence less inhibition of the VA/VL thalamus which leads to less regulation of the motor cortex

Question 4

What 2 pharmacological treatments are commonly used to treat Parkinson’s disease and what is their common side effect?

Answer 4

1. L-Dopa (dopamine pre-cursor)
2. Dopamine agonists
   Side affect: tardative dyskinesia (uncontrolled movements)

Question 5

Name 4 possible surgical treatments of Parkinsons disease

Answer 5

1. Implanting stem cells/ foetal dopamine tissue (improved some patients but made others much worse)
2. Lesions of globus pallidus
3. Deep brain stimulation by implanting electrode designed to release inhibition
4. Gene therapy

Question 6

What brain damage is associated with Alzheimer’s disease?

Answer 6

Starts with entorhinal cortex but spreading to the hippocampus, neocortex and modulatory systems of midbrain and pons

Question 7

What biological signs are associated with Alzheimer’s disease?

Answer 7

• Extracellular plaques formed from the accumulation of 40/42 amino acid beta-amyloid peptide
• Intracellular accumulatin of neurofibrillary tangles made from hyperphophorilated tau

Question 8

What are the beta-amyloid plaques produced by?

Answer 8

Precursor protein APP which is cut by beta-secretase and theta secretase

Question 9

What are 2 drug therapies for Alzheimer’s disease?

Answer 9

• acetylcholinesterase inhibitors

- NMDA receptor agonists

Question 10

What are some studies demonstrating that can reduce beta amyloid levels?

Answer 10

Immunisation by vaccination

Question 11

What is Huntington’s disease caused by?

Answer 11

Entirely genetic, caused by single mutation to chromosome 4 causing protein huntingtin (htt) to be produced

Question 12

What does HT affect?

Answer 12

Predominantly the basal ganglia to produce cognitive and motor problems (uncontrollable movements - chorea)
Formation of inclusion bodies or accumulations of htt

Question 13

What is amyotrophic lateral sclerosis?

Answer 13

Motor neuron disease

• Progressive disorder causing damage to spine and cranial nerves with no cognitive decline
• Death typically 5-10 years after onset
• Riluzole can be used to reduce glutamate neurotoxicity but only extends life by a few months

Question 14

What is multiple sclerosis?

Answer 14

Progressive autoimmune demyelination resulting in a variety of disorders

Question 15

What is the difference between a hemorrhagic stroke and an obstrucitve stroke?

Answer 15

hemorrhagic - burst blood vessel

obstructive - blood vessel blocked

Question 16

How is brain damage caused by a stroke?

Answer 16

• quick depletion of oxygen and glucose leads to ion transporters disrupted and cells becoming depolarised
• glutamate produces a cycle of excitation with cells dying due to excess of Na+ and Ca2+
• damaged mitochondria produce toxic free radicals which attack proteins and DNA