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MD4001 Physiology > Basal Ganglia and Parkinson's Disease > Flashcards

Basal Ganglia and Parkinson's Disease Flashcards

(37 cards)

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1
Q

What structures make up what is known as the basal ganglia?

A
  • Caudate nucleus
  • Putamen
  • Globus pallidus
  • Subthalamic nucleus
  • Subthalamus
  • Substantia nigra
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2
Q

What makes up the neostriatum?

A

Caudate nucleus and putamen

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3
Q

What can the paleostriatum also be known as?

A

Globus pallidus

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4
Q

What are the functions of the basal ganglia?

A
  • Smooth movement
  • Switching behaviour
  • Reward systems
  • Closely linked to thalamus, cortex and limbic system
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5
Q

Describe the motor loop?

A
  • All parts of cerebral cortex project to corpus striatum, basal ganglia project to thalamus, thalamus projects to cerebral cortex
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6
Q

What is the neurotransmitter from cortex to neostriatum?

A

Glutamate (excitatory)

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7
Q

What is the neurotransmitter for neostriatum to globus pallidus?

A

GABA (inhibitory)

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8
Q

What neurotransmitter goes from globus pallidus to thalamus?

A

GABA (inhibitory)

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9
Q

What neurotransmitter goes from the substantia nigra to neostriatum?

A

Dopamine

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10
Q

Stimulation of the direct pathway leads to what?

A

Movement

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11
Q

What is the additional step in the indirect pathway?

A

Globus pallidus (lateral) to subthalamus (via GABA) subthalamus then impinges on the globus palidus (medial)

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12
Q

Describe the direct pathway:

A
  • Cortex to Neostriatum (glutamate)
  • SN to Neostriatum (dopamine)
  • Neostriatum to Globus pallidus (medial) (GABA)
  • Globus Pallidus to Thalamus (GABA)
  • Thalamus to cortex
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13
Q

What does stimulation of the indirect pathway lead to?

A

Inhibition of cortical areas

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14
Q

What are the different dopamine receptors on the neostriatum?

A

D1 - Direct pathway - stimulatory to direct pathway

- D2 - Indirect pathway - Inhibotory of indirect pathway

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15
Q

What does activation of the dopamine pathway lead to?

A
  • Activation of the direct pathway

- Inhibition of the indirect pathway

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16
Q

What area of the basal ganglia has a deficit in Parkinson’s?

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A

Substantia nigra

17
Q

What area of the basal ganglia has a defecit in Huntington’s?

18
Q

What area of the basal ganglia has a defecit in hemiballismus?

19
Q

What area of the basal ganglia has a defecit in Wilson’s disease?

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A

Lentiform nucleus

20
Q

What disease of the basal ganglia is hypokinetic?

Study These Flashcards
A

Parkinson’s

21
Q

What diseases of the basal ganglia are hyperkinetic?

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A
  • Huntington’s disease

- Hemiballismus (violent involuntary movements)

22
Q

What is Wilson’s disease associated with?

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A
  • Copper deposition

- Involuntary movements

23
Q

What are the clinical features of Parkinson’s disease?

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A
  • Tremor at rest
  • Rigidity - cogwheel, limbs>axial
  • Bradykinesia (slowness to initiate movement)
  • Asymmetry
  • Loss righting reflex
  • 30% cognitive decline
  • Hypomimia (lack facial expression)
  • Glabellar tap
  • Quiet speech
  • Micrographia
24
Q

Describe the pathophysiology of Parkinson’s disease in the brain?

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A
  • Degeneration of dopaminergic neurons of substantia nigra
  • Reduction in amount of dopamine being released to neostriatum
  • Lack of D1 activation leads to direct pathway being less activated reduction in inhibtion coming out of neostriatum reduction in inhibition of Globus Paladus medius therefore inhibitory signal coming from neurons is greater leading to greater inhibitory effect on the thalamus therefore less stimulatory output from thalamus to frontal lobe and cerebral cortex. Reduced amount of output coming down to spinal cord
  • Lack of D2 activation indirect pathway also leads to stronger inhibitory signal coming out of neostriatum therefore means greater inhibition on globus palatus lateral thereofre inhibitory effect reduced leading to subthalamus being stimulated which causes globus pallidus medius being increasing its inhibitory output
  • MORE INHIBITION
25
What are the genetics which lead to huntingtons?
- Autosomal dominant - CAG triplet disease(>40 repeats) - Mutant huntintin accumulates, toxic - Chorea, behavioural disorders, dementia - Caudate nucleus wasting
26
Describe the pathophysiology involved in Huntington's disease and how it relates to the direct and indirect pathway?
- Indirect pathway affected - Reduction in inhibitory ouptut (GABA) from neostriatum/caudate nucleus - Globus Palidus (lateral) has an increased Inhibitory (GABA) signal to subthalamus - Subthalamus is over inhibited causing the output of glutamate to be greatly reduced and therefore globus paladus medius is greatly reduced (GABA). Therfore inhibition is reduced from GPM to thalamus. - Stonger signal to cortex and stimulation of muscle contraction -> hyperkinesia
27
What is Wilson's disease?
- Autosomal recessive - Abnormal copper accumulation - Hepato-lenticular degeneration (liver and brain) - Dystonia, ataxia, subcortical dementia - Copper transport protein abnormality - Low serum copper and caeruloplasmin - Kayser-Fleisher rings
28
What is Wilson's disease treated with?
Penicillamine
29
What are the treatment options for Parkinson's (main strategy is to counteract the deficiency in dopamine in the basal ganglia)?
- Levodopa (in combination with carbidopa or benserazide) - Dopamine agonists (e.g. pramipexole, ropinirole and bromocriptine) - Monoamine oxidase B (MAO-B) inhibitors (e.g. selegiline and rasagiline) - Amantadine - releases dopamine - Muscarinic Ach Antagonists (trihexyphenidyl (benzhexol))
30
How does Levodopa indirectly cause an increase in dopamine?
Increases L-Dopa levels which is then converted to dopamine
31
What are some examples of dopamine agonists?
- Pramipexole - Ropinirole - Bromocriptine Increase re-uptake of dopamine
32
What are some examples of mono-amine oxidase inhibitors?
- Selegiline | - Rasagiline
33
How does amantadine function?
- Stimulates release of dopamine and inhibits its re-uptake | - Antiviral drug
34
What drug is the first line treatment for parkinson's disease?
Levodopa combined with dopa decarboxylase inhibitor (carbidopa or benserazide) - prevents side-effects
35
What are the dopamine agonists which act on D1 and D2 receptors?
- Bromocriptine - Cabergoline - Pergolide - Limiting side-effects
36
What are examples of MAO inhibitors?
- Selegiline - Rasagiline Selective MAO-B which lacks unwanted peripheral effects of non-selective MOA inhibitors
37
What are some more experimental treatments for parkinson's?
- Neural transplantation - Stem cell technology - Electrical stimulation of the subthalamic or GPi nuclei by inserted electrodes (DBS) in severe cases. Can improve motor dysfunction. Thought to block output from subthalamus

MD4001 Physiology (22 decks)

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