Effects of estrogen replacement on the relative levels of choline acetyltransferase, trkA, and nerve growth factor messenger RNAs in the basal forebrain and hippocampal formation of adult rats.

Previous studies have shown that estrogen replacement can significantly affect the expression of choline acetyltransferase immunoreactivity (ChAT-IR) and low-affinity (p75NGFR) nerve growth factor receptors within cholinergic neurons located in specific regions of the basal forebrain. To extend this work, we have examined the effects of estrogen replacement on relative levels of choline acetyltransferase (ChAT), trkA, and nerve growth factor (NGF) mRNAs within different regions of the basal forebrain and hippocampal formation using quantitative in situ hybridization techniques. Ovariectomized Sprague-Dawley rats received continuous estrogen replacement for 2 days, 1 week, or 2 weeks. The data show that estrogen replacement results in significant increases in relative cellular levels of ChAT mRNA in the medial septum (MS) and nucleus basalis magnocellularis (nBM), but not in the horizontal limb of the diagonal band of Broca (HDB) or the striatum. In contrast, estrogen replacement resulted in significant decreases in relative levels of NGF mRNA in the hippocampus and of trkA mRNA in the MS and nBM (but not in the HDB or the striatum). The time-course of these effects is consistent with estrogen having a direct effect on ChAT expression which is followed by indirect effects on trkA. The data are also consistent with previous findings in which estrogen replacement resulted in significant increases in ChAT-IR which were followed by significant decreases in p75NGFR mRNA and protein and then a reduction in ChAT-IR back to control levels. Together, these data indicate that estrogen replacement can have significant effects on basal forebrain cholinergic function, and that some of these effects may be mediated by effects of estrogen replacement on the expression of NGF and NGF receptors.