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Brain in Health & Disease > L7 - Parkinson's Disease > Flashcards

L7 - Parkinson's Disease Flashcards

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The Brain flashcards
1
Q

What signals are sent when a load is put on the arm/

A

Spinal reflex

Muscles send signal through dorsal root, extensor and flexor activate and inhibit

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2
Q

How do you catch things?

A

Feed forward control in the primary motor cortex

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3
Q

What part of the brain is for moving parts and how is it arranged>

A

Primary motor cortex

Different sections are for different body parts

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4
Q

What is the circuit of movement in the brain?

A

From neocortex excites caudate which inhibits globus pallidus which inhibits thalamus which excites motor cortex

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5
Q

What are the features of Huntington’s Disease?

A

Symptoms - faster jerky movements
Gene - Huntingtin (Htt) chr4
Mutation - repeats and glutamine
Inter Sympt - Expansion disrupts tramission by reducing transport of vesicles

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6
Q

What happens to the neural circuit in Huntingtons?

A

Caudate neurons degenerate so less inhibition of thalamus so more excitation of cortex = more movement

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7
Q

What are the symptoms of Parkinsons?

A

Hard to initiate and maintain movement

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8
Q

What is the main internal symptom of Parkinsons?

A

Death of dopaminergic substantia nigra neurons

Make lewy bodies

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9
Q

What do Lewy bodies do?

A

Immunoreactive to ubiquitin and a-synuclein

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10
Q

How does a-synuclein become extracellular?

A

By endocytosis

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11
Q

What do the Lewy bodies cause?

A

Dopaminergic neurons in sub-nig die

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12
Q

What is the increase in neuron loss in the sub-nig?

A

4% per decade usually

70-80% loss in Parkinsons

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13
Q

What are the neural circuit results of Parkinsons?

A

Substantia nigra usually affects caudate, so now that inhibits globus pallidus less, which inhibits thalamus more, which excites less motor cortex = less movement

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14
Q

How can you treat Parkinsons?

A 
Oral L-DOPA
Dopamine agonists
MAO-B inhibitors
Cell replacement 
Deep brain stimulation
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15
Q

How the L-DOPA work?

A

Can cross blood-brain barrier and the L stops it from being broken down

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16
Q

What do dopamine agonists do?

A

Mimic the effects of dopamine

17
Q

How do MAO-B inhibitors work?

A

Prevent breakdown of dopamine so sit around in brain longer

18
Q

What is the problem with L-DOPA treatment

A

L-DOPA induced dyskinesia after 5-15 years

Also taken up by serotonin neurons = excessive dopamine release

19
Q

How does deep brain stimulation work?

A

Dopaminergic neurons affected?

20
Q

What is a pharmacological mimic for Parkinsons?

A

6-OH Dopamine

21
Q

What did they do with animal models?

A

Mimiced Parkinsons with pharmalogical mimics

22
Q

What happens when you give animals 6-OH dopamine?

A

Cells don’t like it, and you get loss of dopaminergic neurons

23
Q

What were heroin batches once contaminated with and what happened?

A

MPTP which kills neurons and the addicts came down with Parkinsons

24
Q

What animal can you not give Parkinsons to in the normal way and why?

A

Mouse is not affected by MPTP

25
Q

How does MPTP give Parkinsons?

A 
Turned into MPP+
Activates microglia
Produce RNS's
wnt signalling
further damage
26
Q

What other causes are there?

A

Rotenone (fish poison) blocks mitochondrial function - upregulates a-synuclein
Paraquat

27
Q

What is the Braak hypothesis?

A

dunno

28
Q

How can the action of a-synulcein possibly cause damage?

A

Could go into astrocytes or microglia

29
Q

what are some genetic examples for PD?

A

A-SYNUCLEIN
Parkin (E3 ubiquitin ligase)
DJ-1 (chaperone)

30
Q

What proteins keep mitochondria health?

A

PINK1 and parkin

31
Q

What occurs when mitochondria are slightly damaged?

A

Divide (fission) into healthy half and damaged half (loses all abilities)

32
Q

What does PINK1 do?

A

Binds to damaged mito

33
Q

What does Parkin do?

A

Ubiquitinates PINK1 for degradation (mitophagy)

34
Q

What could combat oxidative stress?

A

GST (glutathione s transferase)

35
Q

What are some gene therapies for the future?

A

GDNF (glial neurotrophic factor)
GAD - mimic GABA
AADC-2 syntehsises DA

Brain in Health & Disease (9 decks)

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