Parkinson's

Question 1

Does the indirect pathway promote or prevent movement?

Answer 1

Prevents

Question 2

Does the direct pathway promote or prevent movement?

Answer 2

Promotes

Question 3

Does DA and the indirect pathway promote or prevent movement?

Answer 3

Promote

Question 4

Does DA and direct pathway promote or prevent movement?

Answer 4

Promote

Question 5

What are the symptoms of Parkinson’s?

Answer 5

Rigidity (resistance to passive movement)
Bradykinesia (slowness of movement once initiated), Resting tremor
Akinesia (absence or reduction of movement)

Question 6

What is the normal output of basal ganglia to thalamus? Why?

Answer 6

Inhibitory to suppress unwanted movements

Question 7

What does DA reinforce in movement?

Answer 7

Initiation

Question 8

What are the SE of directly acting DA Parkinsonian drugs?

Answer 8

Emetic and psychomimetic

Question 9

What happens in Parkinson’s to the neurons?

Answer 9

loss of nigro-striatal dopaminergic pathway this leads to excessive inhibition of thalamo-cortical pathway
Overactivity of STN
Lose neurons that made DA

Question 10

Why type of neurons are basal ganglia full of?

Answer 10

GABA

Question 11

What are the pathological landmarks of Parkinson’s seen in post-mortem?

Answer 11

No Black patch in parkinsons where nigra is.

Lewy bodies are pathological hallmark of parkinsons disease in neurons.

Question 12

What treatments are there for Parkinson’s?

Answer 12

Drugs like L-DOPA
Surgery
DBS - inactivates STN neurons

Question 13

How does DA replacement ameliorate symptoms?

Answer 13

Reduces rigidity and hypokinesia

Question 14

What enzyme is used to metabolise L-DOPA –> DA

Answer 14

DOPA-decarboxylase

Question 15

What negative events happen after being on L-DOPA for a while?

Answer 15

Due to progressive nature of disease, neurones still dying, so cant produce dopamine if wasting. Effectiveness diminishes over 2-5 years. Decrease in dopaminergic nerve terminals leads to decrease in capacity to convert L-DOPA to dopamine. Increase in L-DOPA dose frequency and eventual development of: dyskinesia and on-off effect of sudden transitions between symptom relief and hypokinesia.

Question 16

Apart from L-DOPA what other DA acting agonists are there?

Answer 16

Bromocriptine directly acting DA receptor agonist, non selective.
Pramipexole more D2 receptor selection. Apomorphine which is reserved for advanced stage PD.

Question 17

Bromocriptine

Answer 17

MoA: direct acting DA receptor agonist, non-selective

Question 18

Pramipexole

Answer 18

More D2 receptor agonist selectivity

Question 19

Apomorphine

Answer 19

For advanced stage PD.

Question 20

Selegiline

Answer 20

Selegiline – MAOi (MAOB breaks down dopamine) inhibitor selectively elevates conc of DA

Question 21

Amantidine

Answer 21

Dopamine releaser

Question 22

mAchR antagonists

Answer 22

In striatum produce some symptomatic relief

Question 23

What is L-DOPA given with?

Answer 23

Carbidopa-inhibits the peripheral conversion of L-DOPA to DA.
DOPA decarboxylase inhibitor. Doesn’t cross BBB

Question 24

What does the striatum include?

Answer 24

Striatum will encompass: Caudate nucleus, putamen and nucleus accumbens

Question 25

What are the basal ganglia?

Answer 25

A functional unit, circuit within the brain. Group of associated subcortical nuclei
Integration of sensory and motor information
Cortex -> basal ganglia –> cortex loop
Descending excitatory input from cortex into basal ganglia. Output from basal ganglia through thalamus to cortex.
Not just part of the cortex feeding in, mostly the thinky parts. Pre-frontal cortex sends a lot, sensory less and motor cortex also sending some.
Basal ganglia feed back to Area 6 to the part not necessarily doing the movement but initiating the movement. So motor circuit output to premotor/SMA cortex. Selection and initiation of voluntary movement.