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Lecture 3

BIOL 1F25 Lecture Notes - Lecture 3: Midbrain, Caudate Nucleus, Anatomical Terms Of Motion


Department
Biological Sciences
Course Code
BIOL 1F25
Professor
Gaynor E Spencer
Lecture
3

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BIOL 1F25
DEC 2nd 2015
LEC 3
Treatment of Parkinson’s Disease (PD):
Alternative drug therapy
Tissue graft
Dopamine synthesis:
1st step: conversion of Tyrosine (an amino acid) to DOPA
oCatalyzed by enzyme: Tyrosine Hydroxylase
2nd step: conversion of DOPA to dopamine
Breakdown of dopamine:
1st step: dopamine converted to DOPAL
oCatalyzed by enzyme, Monoamine oxidase B (MAO-B)
2nd step: DOPAL converted to DOPAC
Alternative drug therapy:
MAO-B inhibitors:
inhibit enzyme, monoamine oxidase B (MAO-B), that breaks dopamine down in
cells
slow/ reduce breakdown of dopamine &, thus, help increase dopamine levels
can prolong effect of levodopa therapy
side effects include dyskinesia
tyrosine hydroxylase
tyrosine
tyrosine AA Decarboxylase
DOPA
DOPA
ddopamine
ddopamine
MAO-B
dopamine
dopamine
DOPAAL
DOPAAL
DOPAC
DOPAC
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Tissue grafts
Investigated as an alternative to drug therapy
Desirable in patients for whom chemical therapy no longer works
Goals: reduce need for drug therapy and provide long term/ permanent relief of
PD symptoms
Early experiments on rats were followed by therapy in humans
Challenge:
Replace dead/dying/dysfunctional dopaminergic neurons
How are neurons formed?
Stem cells divide to produce neurons or other stem cells
Neurons and glial cells are formed by different types of stem cells
WHEN are neurons formed (in mammals)?
During fetal development:
oThroughout nervous system
After birth to the end of puberty:
oMany brain regions, but process slows down
In adults:
oSubventricular zone (lining lateral ventricles of the brain)… migrate to
striatum
oSubgranular zone of dentate gyrus (in hippocampus)
oNucleus accumbens
Little formation of new neurons in adults!
How are neurons replaced in adults?
Very badly!!
Once neurons are formed, they don’t divide!
Very few brain regions contain neuronal stem cells that produce new neurons
# of neurons decreases progressively a/f ` 19 years in humans!
Solution:
Implant neural tissue from a host (“grafting” neural tissue)
Early attempts at neural grafting:
b/f 1900: no success
1903-17: Elizabeth Hopkins Dunn transplanted brain cortex tissue b/w 10 day old
rats- tissue survived in 10% of cases
1940s: W.E LeGros Clark transplanted brain tissue from rabiit embryos to 6 week
old rabbits
oTransplanted neurons survived & matured
Embryonic brain tissue contains stem cells & immature neurons
Stem cells & embryonic neurons survive transplantation better than mature brain tissue!
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