Huntingtons

Question 1

What is chorea?

Answer 1

dancelike movement

Question 2

What is athetosis?

Answer 2

slow convoluted writhing movements

Question 3

What are extrapyrimidal movements?

Answer 3

reflexes and movements. movement modulation

Question 4

What are the disease characteristics?

Answer 4

cognitive decline and emotional disturbances
15 year progression to incapacitation
sufferers often succumb to aspiration pneumonia

Question 5

What is the gene that has gone wrong in huntingtons?

Answer 5

CAG. The glutamine coding area

Question 6

What are the different genetic ranges for huntingtons?

Answer 6

-35 CAG repeats = normal
35-40 CAG repeats = carrier
40 - CAG repeats = huntingtons

Question 7

Does it matter how long the CAG repeats are?

Answer 7

Yes it is graded. The longer the CAG sequence the earlier the onset and the more severe the symptoms

Question 8

longer sequence people are likely to have inherited the gene from their

Answer 8

father

Question 9

What does the CAG code for?

Answer 9

the htt protein

Question 10

What does the htt protein do?

Answer 10

large protein. has antiapoptotic qualities

Question 11

What are inclusions?

Answer 11

accumulations of the htt protein that are heavily unbiquinated

Question 12

What is the macroscopic pathology of huntingtons?

Answer 12

marked cerebral atrophy

atrophy of the caudate nucleus, putamen and globes pallidus

Question 13

What is the microscopic pathology of huntingtons?

Answer 13

Neurons that use GABA are preferentially affected. Called Medium spiny neurons. Make up 95% of the striatum

Question 14

What is the vonsattel pathology grading system?

Answer 14

A post mortem grading system of huntingtons
grade 0 - no change
grade 1 - 50% loss of MSNs
grade 2-3 - major loss of MSNs
grade 4 - 80% loss of MSNs and cortical shrinkage

Question 15

What MSNs are lost early?

Answer 15

ones containing enkephalin and CB1

Question 16

What MSNs are lost later?

Answer 16

Ones containing substance P and CB1

Question 17

What is the flow chart of how huntingtons works?

Answer 17

The neurons from the striatum to the GPE die off. these are inhibitory neurons.
There is no inhibition on the inhibitory neurons projecting to the subthalamic nucleus.
The firing of the inhibitory neurons projecting to the subthalamis nucleus increases.
Therefore there is decreased firing of the excitatory neurons leading to the GPI.
Therefore there is less inhibiton of the neurons from the GPI to the frontal cortex. these neurons fire more and therefore there is more movement.