Flashcards in L7 - Parkinson's Disease Deck (35):
What signals are sent when a load is put on the arm/
Muscles send signal through dorsal root, extensor and flexor activate and inhibit
How do you catch things?
Feed forward control in the primary motor cortex
What part of the brain is for moving parts and how is it arranged>
Primary motor cortex
Different sections are for different body parts
What is the circuit of movement in the brain?
From neocortex excites caudate which inhibits globus pallidus which inhibits thalamus which excites motor cortex
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
What happens to the neural circuit in Huntingtons?
Caudate neurons degenerate so less inhibition of thalamus so more excitation of cortex = more movement
What are the symptoms of Parkinsons?
Hard to initiate and maintain movement
What is the main internal symptom of Parkinsons?
Death of dopaminergic substantia nigra neurons
Make lewy bodies
What do Lewy bodies do?
Immunoreactive to ubiquitin and a-synuclein
How does a-synuclein become extracellular?
What do the Lewy bodies cause?
Dopaminergic neurons in sub-nig die
What is the increase in neuron loss in the sub-nig?
4% per decade usually
70-80% loss in Parkinsons
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
How can you treat Parkinsons?
Deep brain stimulation
How the L-DOPA work?
Can cross blood-brain barrier and the L stops it from being broken down
What do dopamine agonists do?
Mimic the effects of dopamine
How do MAO-B inhibitors work?
Prevent breakdown of dopamine so sit around in brain longer
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
How does deep brain stimulation work?
Dopaminergic neurons affected?
What is a pharmacological mimic for Parkinsons?
What did they do with animal models?
Mimiced Parkinsons with pharmalogical mimics
What happens when you give animals 6-OH dopamine?
Cells don't like it, and you get loss of dopaminergic neurons
What were heroin batches once contaminated with and what happened?
MPTP which kills neurons and the addicts came down with Parkinsons
What animal can you not give Parkinsons to in the normal way and why?
Mouse is not affected by MPTP
How does MPTP give Parkinsons?
Turned into MPP+
What other causes are there?
Rotenone (fish poison) blocks mitochondrial function - upregulates a-synuclein
What is the Braak hypothesis?
How can the action of a-synulcein possibly cause damage?
Could go into astrocytes or microglia
what are some genetic examples for PD?
Parkin (E3 ubiquitin ligase)
What proteins keep mitochondria health?
PINK1 and parkin
What occurs when mitochondria are slightly damaged?
Divide (fission) into healthy half and damaged half (loses all abilities)
What does PINK1 do?
Binds to damaged mito
What does Parkin do?
Ubiquitinates PINK1 for degradation (mitophagy)
What could combat oxidative stress?
GST (glutathione s transferase)