Estrogen replacement does not prevent the loss of choline acetyltransferase-positive cells in the basal forebrain following either neurochemical or mechanical lesions

Abstract

Recent studies have shown that estrogen replacement can enhance the functional status of basal forebrain cholinergic neurons. Studies have also shown that estrogen has neuroprotective effects both in vitro and in vivo on a variety of cells and against a variety of insults. The present study examined the ability of estrogen replacement to protect basal forebrain cholinergic neurons from the effects of neurochemical and mechanical injury. Ovariectomized Sprague–Dawley rats received either estrogen replacement or sham surgery, and then received either a unilateral injection of ibotenic acid into the nucleus basalis magnocellularis, or unilateral transection of the fimbria fornix. Cholinergic neurons in the medial septum and nucleus basalis were detected and quantified using immunohistochemical techniques. The data show that neither 3 weeks nor 13 weeks of continuous estrogen replacement prevented the loss of choline acetyltransferase (ChAT)-containing cells in the nucleus basalis following a unilateral injection of ibotenic acid. Likewise, estrogen replacement did not prevent a decrease in ChAT-positive cells detected in the medial septum following unilateral transection of the fimbria fornix. Notably, increased numbers of ChAT-positive cells were detected in the contralateral nucleus basalis, and in the ipsilateral and contralateral medial septum, at 2 weeks following a unilateral injection of ibotenic acid into the nucleus basalis; however, these effects were not related to hormone treatment. These data suggest that estrogen replacement does not protect cholinergic neurons in the medial septum and nucleus basalis from the effects of excitotoxic or mechanical injury.