NGF trkA and p75
Introduction
Introduction
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<strong>NGF</strong><br />
Advance aging <strong>and</strong> AD brain<br />
Basal forebrain<br />
cholinergic neuron<br />
Hippocampus<br />
Medial septum<br />
<strong>NGF</strong> mRNA<br />
<strong>NGF</strong> protien <strong>and</strong> precursor pro-<strong>NGF</strong><br />
P75,Trk<br />
P75,Trk<br />
receptor<br />
Advancing age<br />
- levels of <strong>NGF</strong> mRNA in the<br />
hippocampus <strong>and</strong> cortex remain unaltered<br />
- protein levels of both <strong>NGF</strong> <strong>and</strong> its<br />
precursor pro-<strong>NGF</strong> are reported to increase<br />
- In contrast, immunoreactivity for <strong>NGF</strong><br />
receptor proteins <strong>trkA</strong> <strong>and</strong> <strong>p75</strong> in the medial<br />
septum of aged rats is reduced significantly<br />
= Similar findings have been reported<br />
from studies of AD brains<br />
7<br />
8<br />
<strong>NGF</strong><br />
• Neurotrophins -> family of CNS expressed<br />
proteins<br />
<strong>trkA</strong> <strong>and</strong> <strong>p75</strong><br />
trk = high affinity tyrosine kinase (<strong>trkA</strong>)<br />
P75 = low affinity <strong>p75</strong> receptor<br />
Suggest that a defect in the retrograde<br />
transport of <strong>NGF</strong> from cholinergic target<br />
regions is responsible for the degeneration<br />
of BFCN seen in both aging <strong>and</strong> AD<br />
9<br />
10<br />
Transcription of <strong>p75</strong> <strong>and</strong> <strong>trkA</strong> is partly<br />
under the influence of <strong>NGF</strong> itself thus,<br />
defective transport of <strong>NGF</strong> from the<br />
hippocampus to the medial septum may<br />
account for the reduction of <strong>p75</strong> <strong>and</strong> <strong>trkA</strong><br />
protein in the basal forebrain<br />
11<br />
Hidden platform version of the Morris<br />
water maze<br />
- demonstrate cognitive deficits in aged<br />
rodents<br />
- hippocampus-dependent memory<br />
task<br />
Several studies have shown that age-<br />
related impairments in spatial learning<br />
in the water maze are present in rats<br />
with reduced cholinergic neuron number<br />
or size<br />
12
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