Basal Ganglia and Cerebellum II Flashcards
What are the main characteristics of Huntington’s disease?
Neurodegenerative condition.
Autosomal Dominant
Selective loss of medium spiny neurons in striatum
(rare)
What happens in early Huntington’s disease?
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
What drug can be used to manage ‘mood disturbances’ in Huntington’s disease?
Anti-psychotic
What drug can be used to manage ‘impulsiveness and aggression’ in Huntington’s disease?
Anti-epileptics i.e. valproate
What drug can be used to manage ‘dystonia and myoclonus’ in Huntington’s disease?
Anti-spasticity and anti-parkinsons drugs
What drug can be used to manage ‘chorea’ in Huntington’s disease?
Dopamine blocking agents - can reduce the effect of inhibitory indirect pathway
How could cell transplantation work to reduce symptoms of/ cure Huntington’s disease?
Where would you source these cells from?
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
What is a benefit from using cells from human foetal tissue for transplantation?
Improves motor function and cognition
How does antisense oligonucleotide therapy work?
Synthetic drug and binds to mRNA produced at faulty gene and it stops it from being bound to protein
What is the end result of antisense oligonucleotide therapy?
Mutant Huntington’s diseased cells are reduced over time with different dosages
What is the function of the cerebellum?
Regulation of voluntary movement
Motor learning and behaviour
Posture, balance, motor co-ordination and speech
What are the 3 main lobes of the cerebellum?
Anterior, posterior and flocculonodular lobe
What is the flocculonodular lobe?
Made of nodulus and flocculus - first in evolutionary tree to form
Involved in balancing the head and eye
Where is the anterior lobe located and what does it do?
At the top of the cerebellum - involved in muscle tone
What is the posterior lobe?
At the bottom of the cerebellum - appeared last evolution wise
To do with co-ordination of movement
Other name for archicerebellum?
Vestibulocerebellum
Other name for paleocerebellum?
Spinocerebellum
Other name for Neocerebellum?
Cerebrocerebellum
What are the inputs to the cerebellum?
Ascending spinal tracts
Brainstem
Cortex via brainstem and midbrain regions
What are the outputs of the cerebellum?
Cortex (Cerebrocerebellum)
Spine (Spinocerebellum)
Balance and eye movements (vestibulocerebellum)
What does the vestibulo-occular reflex do?
Maintains eye on visual target when head is rotated (gaze)
What does the vestibulo-occular reflex do?
Maintains eye on visual target when head is rotated (gaze)
What are the common symptoms experienced with damage to the cerebellum?
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 )
What is hereditary ataxia?
Autosomal recessive disease due to expansion of GAA trinucleotide repeat in intron of FRDA gene
What happens at a molecular level in hereditary ataxia?
4 marks
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
What is ataxia?
Lack of co-ordinated voluntary movement
What are the characteristics of spinocerebellar ataxia type 1?
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
