Document Detail


The effects of ovariectomy and estrogen replacement on trkA and choline acetyltransferase mRNA expression in the basal forebrain of the adult female Sprague-Dawley rat.
MedLine Citation:
PMID:  8774454     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cognitive deficits associated with aging and with neurodegenerative diseases such as Alzheimer's disease have been attributed to degeneration of cholinergic neurons in the basal forebrain. Estrogen is known to provide trophic support to cholinergic neurons, although the mechanisms underlying the actions of estrogen have yet to be determined. Because cholinergic neurons require neurotrophic growth factors for their survival, it is possible that the trophic effects of estrogen on basal forebrain systems are caused by enhanced expression of neurotrophins or their receptors. To begin to examine this hypothesis, we used in situ hybridization analysis to determine the effects of ovariectomy (ovx) and estrogen replacement on trkA mRNA levels in the rat basal forebrain. Ten days of estrogen deprivation after ovx resulted in significant decreases in trkA mRNA levels in the horizontal limb of the diagonal band of Broca and the nucleus basalis of Meynert. Short-term estrogen replacement therapy restored trkA mRNA expression to a level comparable with ovary-intact animals. No changes in trkA mRNA levels were observed in the vertical limb of the diagonal band of Broca after ovx or estrogen replacement. To assess the functional status of cholinergic neurons in the absence and presence of estrogen, the effects of ovx and estrogen replacement on ChAT mRNA levels were also examined and found to reflect the changes observed in trkA mRNA expression. These studies suggest that the trophic effects of estrogen on basal forebrain cholinergic systems may be mediated, in part, through the signaling of neurotrophic growth factors through their receptors.
Authors:
P J McMillan; C A Singer; D M Dorsa
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  16     ISSN:  0270-6474     ISO Abbreviation:  J. Neurosci.     Publication Date:  1996 Mar 
Date Detail:
Created Date:  1997-01-03     Completed Date:  1997-01-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1860-5     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Washington, Seattle 98195, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carrier Proteins / genetics*
Choline O-Acetyltransferase / genetics*
Estrogens / pharmacology*
Female
In Situ Hybridization
Membrane Proteins / genetics*
Ovariectomy*
Prosencephalon / metabolism*
RNA, Messenger / metabolism*
Rats
Rats, Sprague-Dawley
Receptor, trkA*
Grant Support
ID/Acronym/Agency:
AG05136/AG/NIA NIH HHS; HDO7453-01/HD/NICHD NIH HHS; NS20311/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Estrogens; 0/Membrane Proteins; 0/RNA, Messenger; EC 2.3.1.6/Choline O-Acetyltransferase; EC 2.7.10.1/Receptor, trkA

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