Basal Ganglia and Cerebellum II

Question 1

What are the main characteristics of Huntington’s disease?

Answer 1

Neurodegenerative condition.
Autosomal Dominant
Selective loss of medium spiny neurons in striatum
(rare)

Question 2

What happens in early Huntington’s disease?

Answer 2

Loss of medium spiny neurons in striatum so can’t inhibit GPe - so it’s activated and will send inhibitory projections to STN which means it cannot excite GPi, therefore there are no inhibitory projections to the thalamus causing jerky and dancing movement

Question 3

What drug can be used to manage ‘mood disturbances’ in Huntington’s disease?

Answer 3

Anti-psychotic

Question 4

What drug can be used to manage ‘impulsiveness and aggression’ in Huntington’s disease?

Answer 4

Anti-epileptics i.e. valproate

Question 5

What drug can be used to manage ‘dystonia and myoclonus’ in Huntington’s disease?

Answer 5

Anti-spasticity and anti-parkinsons drugs

Question 6

What drug can be used to manage ‘chorea’ in Huntington’s disease?

Answer 6

Dopamine blocking agents - can reduce the effect of inhibitory indirect pathway

Question 7

How could cell transplantation work to reduce symptoms of/ cure Huntington’s disease?

Where would you source these cells from?

Answer 7

Replace damaged medium spiny neurons with healthy ones.

Whole ganglionic eminences - from embryo. Tissue processed and transplanted into brain. Or stem cells. If cells transplanted and grafted well, can restore cells in the brain

Question 8

What is a benefit from using cells from human foetal tissue for transplantation?

Answer 8

Improves motor function and cognition

Question 9

How does antisense oligonucleotide therapy work?

Answer 9

Synthetic drug and binds to mRNA produced at faulty gene and it stops it from being bound to protein

Question 10

What is the end result of antisense oligonucleotide therapy?

Answer 10

Mutant Huntington’s diseased cells are reduced over time with different dosages

Question 11

What is the function of the cerebellum?

Answer 11

Regulation of voluntary movement
Motor learning and behaviour
Posture, balance, motor co-ordination and speech

Question 12

What are the 3 main lobes of the cerebellum?

Answer 12

Anterior, posterior and flocculonodular lobe

Question 13

What is the flocculonodular lobe?

Answer 13

Made of nodulus and flocculus - first in evolutionary tree to form
Involved in balancing the head and eye

Question 14

Where is the anterior lobe located and what does it do?

Answer 14

At the top of the cerebellum - involved in muscle tone

Question 15

What is the posterior lobe?

Answer 15

At the bottom of the cerebellum - appeared last evolution wise
To do with co-ordination of movement

Question 16

Other name for archicerebellum?

Answer 16

Vestibulocerebellum

Question 17

Other name for paleocerebellum?

Answer 17

Spinocerebellum

Question 18

Other name for Neocerebellum?

Answer 18

Cerebrocerebellum

Question 19

What are the inputs to the cerebellum?

Answer 19

Ascending spinal tracts
Brainstem
Cortex via brainstem and midbrain regions

Question 20

What are the outputs of the cerebellum?

Answer 20

Cortex (Cerebrocerebellum)
Spine (Spinocerebellum)
Balance and eye movements (vestibulocerebellum)

Question 21

What does the vestibulo-occular reflex do?

Answer 21

Maintains eye on visual target when head is rotated (gaze)

Question 22

What does the vestibulo-occular reflex do?

Answer 22

Maintains eye on visual target when head is rotated (gaze)

Question 23

What are the common symptoms experienced with damage to the cerebellum?

Answer 23

Hypotonia - low level of muscle tone
Ataxia - lack of co-ordination of voluntary movement
Action or intention tremors (tremor at the end of a movement )

Question 24

What is hereditary ataxia?

Answer 24

Autosomal recessive disease due to expansion of GAA trinucleotide repeat in intron of FRDA gene

Question 25

What happens at a molecular level in hereditary ataxia?

4 marks

Answer 25

Decrease in protein faxin.

Iron accumulation in mitochondria which leas to excess free radicals.

Fibre loss in dorsal columns and spinocerebellar tracts.

Cellular damage and death

Question 26

What is ataxia?

Answer 26

Lack of co-ordinated voluntary movement

Question 27

What are the characteristics of spinocerebellar ataxia type 1?

Answer 27

Autosomal dominant (expanded CAG repeat in chromosome 6 containing SCA1 locus)
Correlation in (CAG)n size and age of onset
Neurodegeneration of cerebellum, spinal cord and brainstem