Brain Mechanisms of Movement II

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• Brain Mechanisms of Movement II
• Movement Disorders (8.3)
• Disorders of the spinal column
• Parkinsons Disease
• Huntingtons Disease

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Disorders of the Spinal Column
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Disorders of the Spinal Column
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• Movement Disorders Parkinsons Disease
• symptoms muscle rigidity, muscle tremors, slow
  movements, difficulty initiating physical and
  mental activity
• consequences depression, cognitive decline
• lt 50 y fairly uncommon (strong genetic basis
  familial heritability twin studies)
• early onset mutation of 3 genes produces
  deviant forms of three proteins parkin,
  ubiquitin, a-synuclein (produces Lewy bodies -
  clumps of protein)
• gt 50 affects 1 in 100 (unknown etiology)
• affects the brain extensive loss of dopaminergic
  neurons in the substantia nigra and amygdala

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• Treatment Options
• L-Dopa Treatment
• precursor for dopamine which can cross the
  blood-brain barrier
• individual differences in effectiveness
• does not stop progression of the disease
• numerous side effects (nausea, restlessness,
  sleep problems, low blood pressure, and
  hallucinations) related to increased
  dopaminergic activity throughout the brain)
• less helpful in the later stages
• Therapies Other Than L-Dopa
• dopamine receptor stimulants, neurotrophins or
  drugs that decrease apoptosis
• antioxidants
• inactive the globus pallidus (electrical or
  surgical)
• tissue transplants (target just the amygdala and
  SN first trials - not promising)
• Odd facts...
• drinking caffeine can decrease risk up to 80
• smoking can decrease risk up to 50

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• Movement Disorders Huntingtons Disease
• symptoms uncontrolled movements (facial twitch,
  tremors, writhing movements), speech problems,
  depression, memory impairment, anxiety,
  hallucinations
• affects 1 in 10,000 people
• age of onset 30-50y disease progresses over
  15y culminates in death
• affects the brain produces gradual, widespread
  brain damage greatest degeneration occurs in the
  caudate/putamen, globus pallidus, cortex

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Healthy Brain
Huntingtons Disease
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• Cause of Huntingtons Disease is Known
• produced by a mutation of a dominant autosomal
  gene on chromosome 4
• heritable 50 transmission to children
• mutation increases production of huntingtin, a
  protein that is incorporated into cells and
  causes cell death or disrupts the normal
  functioning of the affected cells
• mutation increases a C-A-G sequence repeat
  (normal 11-24 times)
• age of onset can be determined by the number of
  C-A-G repeats

• Treatment Option
• transplant of embryonic cells
• inject fetal striatum cells into brain of
  Huntingtons patient
• 18 months post-surgery cells had incorporated
  into 10 of the striatum
• no evidence of huntingtin protein