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 significantl y affect the expression of choline acetyltransferase immunoreactivity (ChAT-IR) and low-affinity (p75(NGFR)) nerve growth factor receptors w ithin cholinergic neurons located in specific regions of the basal for ebrain. To extend this work, we have examined the effects of estrogen replacement on relative levels of choline acetyltransferase (ChAT), tr kA, and nerve growth factor (NGF) mRNAs within different regions of th e 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 d ata show that estrogen replacement results in significant increases in relative cellular levels of ChAT mRNA in the medial septum (MS) and n ucleus basalis magnocellularis (nBM), but not in the horizontal limb o f the diagonal band of Broca (HDB) or the striatum. In contrast, estro gen replacement resulted in significant decreases in relative levels o f 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 c onsistent with estrogen having a direct effect on ChAT expression whic h is followed by indirect effects on trkA. The data are also consisten t with previous findings in which estrogen replacement resulted in sig nificant increases in ChAT-IR which were followed by significant decre ases in p75(NGFR) mRNA and protein and then a reduction in ChAT-IR bac k to control levels. Together, these data indicate that estrogen repla cement can have significant effects on basal forebrain cholinergic fun ction, and that some of these effects may be mediated by effects of es trogen replacement on the expression of NGF and NGF receptors. (C) 199 4 Academic Press, Inc.