14 - Parkinson's Disease & Parkinsonism

Question 1

List the symptoms of Parkinson’s disease…

Answer 1

• Motor symptoms
  
  • Resting tremor
  • Muscle rigidity
  • Suppression of voluntary movement
• Cognitive symptoms

Question 2

Post-mortem neuropathology reveals the loss of _______ cell bodies in the ________ ______

Answer 2

Post-mortem neuropathology reveals the loss of dopamine cell bodies in the substantia nigra

Question 3

Degeneration of dopaminergic neurones in the nigrostriatal tract leads to a loss of dopamine neurotransmission in the _______

Answer 3

Degeneration of dopaminergic neurones in the nigrostriatal tract leads to a loss of dopamine neurotransmission in the striatum

Question 4

Conditions other than Parkinson’s Disease which lead to the loss of dopamine neutrotransmission in the striatum are known as…

Answer 4

Parkinsonism

Question 5

The loss of dopamine leads to a lack of inhibition, which:

a) increases transmission by D₂ receptors
b) decreases transmission by D₂ receptors
c) increases transmission by D₆ receptors
d) decreases transmission by D₆ receptors

Answer 5

The loss of dopamine leads to a lack of inhibition, which:

a) increases transmission by D₂ receptors

b) decreases transmission by D₂ receptors
c) increases transmission by D₆ receptors
d) decreases transmission by D₆ receptors

Question 6

Outline how dopamine is synthesised, starting from tyrosine inside the presynaptic cell (2)…

Answer 6

1. Tyrosine is converted to L-DOPA by tyrosine hydroxylase*
2. L-DOPA is converted to Dopamine by DOPA decarboxylase

*Rate limiting step

Question 7

Dopamine reuptake occurs via…

Answer 7

DAT (DopAmine Transporter)

Question 8

MAO metabolises dopamine that is not in vesicles. The main metaboliser of dopamine is…

a) MAO_A
b) MAO_B
c) DAT
d) ACE

Answer 8

MAO metabolises dopamine that is not in vesicles. The main metaboliser of dopamine is…

a) MAO_A

b) MAO_B

c) DAT (reuptake of dopamine)
d) ACE (metabolism of acetyl choline)

Question 9

Dopamine receptors are linked to:

a) ion channels
b) NMJ
c) G-proteins
d) all of the above

Answer 9

Dopamine receptors are linked to:

a) ion channels
b) NMJ

c) G-proteins

d) all of the above

Question 10

D1 receptors are (excitatory / inhibitory) - they (stimulate / inhibit) adenyl cyclase and open potassium channels (hyperpolarising effect)

D2 receptors are (excitatory / inhibitory) - they (stimulate / inhibit) adenyl cyclase

Answer 10

D1 receptors are inhibitory - they inhibit adenyl cyclase and open potassium channels (hyperpolarising effect) (Gi)

D2 receptors are excitatory - they stimulate adenyl cyclase (Gs)

Question 11

Why is supplementation of tyrosine an inneffective way of increasing dopamine levels?

Answer 11

Because conversion of tyrosine to L-DOPA by tyrosine hydroxylase is the rate limiting step in the production of dopamine

Question 12

Supplementation with L-DOPA may increase dopamine levels. However, most of it is processed by peripheral DOPA decarboxylase before reaching the target site. This can be counteracted using…

Answer 12

An inhibitor of peripheral DOPA decarboxylase (such as carbidopa)

Question 13

Why can’t Parkinson’s disease be treated by supplementation of dopamine itself?

Answer 13

• Dopamine is a polar molecule thus unable to cross membranes without transporters (of which there are none)
• Metabolised in the gut by MAO

Question 14

Dopamine levels can also be raised by targeting the metabolism of dopamine.

Give an example of a drug that does this…

Answer 14

Selegiline (a MAO_B inhibitor)

Question 15

Another way to increase dopaminergic transmission is to mimic dopamine with an alternative D2 receptor agonist, such as…

Answer 15

Bromocriptine or Apomorphine

(methods that raise endogenous dopamine levels are used first, then exogenous agonists are added as pre-neurone dies)

Question 16

Iatrogenic (drug-caused) Parkisonism can be caused by which medications?

Answer 16

Anti-psychotics for schizophrenia _{(associated with excessive D2 activity)} reduce D₂ activity by blocking D₂ via all 4 pathways.