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

Pamela J. McMilian, Cherie A. Singer, Daniel Dorsa

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1860-1865
Number of pages6
JournalJournal of Neuroscience
Volume16
Issue number5
StatePublished - Mar 1 1996
Externally publishedYes

Fingerprint

Estrogen Replacement Therapy
Choline O-Acetyltransferase
Ovariectomy
Sprague Dawley Rats
Estrogens
Cholinergic Neurons
Messenger RNA
Nerve Growth Factors
Diagonal Band of Broca
Intercellular Signaling Peptides and Proteins
Extremities
Basal Nucleus of Meynert
Neurodegenerative Diseases
Cholinergic Agents
In Situ Hybridization
Basal Forebrain
Ovary
Alzheimer Disease

Keywords

  • basal forebrain
  • ChAT
  • cholinergic neurons
  • estrogen
  • neurotrophins
  • trkA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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. / McMilian, Pamela J.; Singer, Cherie A.; Dorsa, Daniel.

In: Journal of Neuroscience, Vol. 16, No. 5, 01.03.1996, p. 1860-1865.

Research output: Contribution to journalArticle

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