L7 - Parkinson's Disease Flashcards Preview

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

Flashcards in L7 - Parkinson's Disease Deck (35):
1

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

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

2

How do you catch things?

Feed forward control in the primary motor cortex

3

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

Primary motor cortex
Different sections are for different body parts

4

What is the circuit of movement in the brain?

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

5

What are the features of Huntington's Disease?

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

6

What happens to the neural circuit in Huntingtons?

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

7

What are the symptoms of Parkinsons?

Hard to initiate and maintain movement

8

What is the main internal symptom of Parkinsons?

Death of dopaminergic substantia nigra neurons
Make lewy bodies

9

What do Lewy bodies do?

Immunoreactive to ubiquitin and a-synuclein

10

How does a-synuclein become extracellular?

By endocytosis

11

What do the Lewy bodies cause?

Dopaminergic neurons in sub-nig die

12

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

4% per decade usually
70-80% loss in Parkinsons

13

What are the neural circuit results of Parkinsons?

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

14

How can you treat Parkinsons?

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

15

How the L-DOPA work?

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

16

What do dopamine agonists do?

Mimic the effects of dopamine

17

How do MAO-B inhibitors work?

Prevent breakdown of dopamine so sit around in brain longer

18

What is the problem with L-DOPA treatment

L-DOPA induced dyskinesia after 5-15 years
Also taken up by serotonin neurons = excessive dopamine release

19

How does deep brain stimulation work?

Dopaminergic neurons affected?

20

What is a pharmacological mimic for Parkinsons?

6-OH Dopamine

21

What did they do with animal models?

Mimiced Parkinsons with pharmalogical mimics

22

What happens when you give animals 6-OH dopamine?

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

23

What were heroin batches once contaminated with and what happened?

MPTP which kills neurons and the addicts came down with Parkinsons

24

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

Mouse is not affected by MPTP

25

How does MPTP give Parkinsons?

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

26

What other causes are there?

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

27

What is the Braak hypothesis?

dunno

28

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

Could go into astrocytes or microglia

29

what are some genetic examples for PD?

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

30

What proteins keep mitochondria health?

PINK1 and parkin

31

What occurs when mitochondria are slightly damaged?

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

32

What does PINK1 do?

Binds to damaged mito

33

What does Parkin do?

Ubiquitinates PINK1 for degradation (mitophagy)

34

What could combat oxidative stress?

GST (glutathione s transferase)

35

What are some gene therapies for the future?

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