Date of Award

Summer 1997

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Neuroscience

Committee Director

Francis J. Liuzzi

Committee Member

David E. Scott

Committee Member

Cjarles W. Morgan

Committee Member

Keith A. Carson

Abstract

Skin sensation is mediated by dorsal root ganglion (DRG) neurons. Data indicates that skin sensitivity in female rats is estrogen-dependent. Some DRG neurons have estrogen receptors (ERs) which are regulated by estrogen. In these cells, nerve growth factor (NGF) and estrogen receptors colocalize. Regulation of NGF receptors and neuronal sensitivity to NGF may allow estrogen to regulate NGF-dependent genes. The goals of the present study were to determine which DRG neurons express the ER gene and to analyze the effects of long-term estrogen administration on the interrelated expression of tyrosine kinase A (trkA), preprotachykinin (PPT), and 68kD neurofilament (NF) genes and to compare warm thermal withdrawal latencies in these animals. The hypothesis tested by the current study was that estrogen upregulates trkA and by doing so, increases the sensitivity of NGF-receptive neurons to the growth factor.

Three groups of ovariectomized (OVX) Sprague-Dawley rats were used: OVX (no replacement), 1X (low dose) and 10X (high dose). The replacement groups received daily Premarin injections. Rats from each group were killed at 56 or 90 days and their lumbar DRGs harvested.

ER mRNA localization was done by in situ hybridization. Results showed that ER mRNA was of low abundance, but was evident in smaller neurons. Quantification revealed that both trkA and PPT mRNA was downregulated in both estrogen replacement groups at both time points when compared to the OVX group. TrkA mRNA was localized predominantly in small DRG neurons. PPT mRNA was restricted to small neurons. Estrogen treatment slowed warm thermal plantar withdrawal, but not significantly. Neurofilament mRNA levels were dramatically increased by 56 days of estrogen treatment in a dose-dependent manner in all size populations of DRG neurons. Ninety days of estrogen treatment had a similar effect.

These data indicate that estrogen regulates DRG neuronal gene expression. An overlapping population of DRG neurons express the ER, trkA and PPT genes. Estrogen may regulate the trkA and PPT genes by altering NGF sensitivity. Since the ER gene does not appear to be expressed by all DRG neurons, the effect of estrogen on neurofilament gene expression must involve alternative mechanisms.

Comments

A Dissertation Submitted to the Faculties of Eastern Medical School and Old Dominion University in {artial Fulfillment of the Requirements for the Degree of doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/j8cr-je96

ISBN

9780591603958

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