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

Recent studies have shown that estrogen replacement can enhance the functio nal status of basal forebrain cholinergic neurons. Studies have also shown that estrogen has neuroprotective effects both in vitro and in vivo on a va riety 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. Ovariecto mized Sprague-Dawley rats received either estrogen replacement or sham surg ery, and then received either a unilateral injection of ibotenic acid into the nucleus basalis magnocellularis, or unilateral transection of the fimbr ia fornix. Cholinergic neurons in the medial septum and nucleus basalis wer e detected and quantified using immunohistochemical techniques. The data sh ow that neither 3 weeks nor 13 weeks of continuous estrogen replacement pre vented the loss of choline acetyltransferase (ChAT)-containing cells in the nucleus basalis following a unilateral injection of ibotenic acid. Likewis e, estrogen replacement did not prevent a decrease in ChAT-positive cells d etected in the medial septum following unilateral transection of the fimbri a fornix. Notably, increased numbers of ChAT-positive cells were detected i n the contralateral nucleus basalis, and in the ipsilateral and contralater al medial septum, at 2 weeks following a unilateral injection of ibotenic a cid into the nucleus basalis; however, these effects were not related to ho rmone treatment. These data suggest that estrogen replacement does not prot ect cholinergic neurons in the medial septum and nucleus basalis from the e ffects of excitotoxic or mechanical injury. (C) 2000 Elsevier Science B.V. All rights reserved.