17-BETA-ESTRADIOL ATTENUATES FIMBRIAL LESION-INDUCED DECLINE OF CHAT-IMMUNOREACTIVE NEURONS IN THE RAT MEDIAL SEPTUM

We investigated the neuroprotective effects of 17 beta-estradiol (E-2) on medial septal cholinergic neurons following partial unilateral les ion of the fimbria-fornix. Adult female rats were ovariectomized (OVX) and, 5 days later, treated with a single intravenous (iv) injection o f an estradiol (E-2)-chemical delivery system (E-2-CDS) or its vehicle hydroxypropyl-beta-cyclodextrin (HPCD). All rats were subjected to pa rtial unilateral electrolytic fimbrial lesion the following day. At 20 days postlesion, brain slices from treated animals were assessed for choline acetyltransferase (ChAT) by immunohistochemistry. Animals trea ted with HPCD or E-2-CDS showed a 44 or 4% decrease, respectively, in ChAT-positive neurons on the lesioned side compared to the nonlesioned side of the medial septum. In a second study using the same lesioning procedure, adult OVX rats received either a subcutaneous E-2 pellet i mplant (n = 6), or, 5 days postovariectomy, a single iv injection of E -2-CDS (n = 8) or HPCD (n = 6). Animals treated with HPCD showed a 55% decrease in ChAT-positive neurons on the lesioned side compared to th e nonlesioned side of the medial septum. By contrast, rats treated wit h E-2-CDS or E-2 pellet had a 14 or 13% decrease, respectively, in ChA T-positive neurons. Interestingly, E-2 treatment substantially decreas ed ChAT-positive neurons on the nonlesioned side of the medial septum in comparison to control animals. The present study suggests that chol inergic neurons in the medial septum are protected from lesion-induced degeneration by treatments which increase brain E-2 levels. Thus, E-2 may play a neuroprotective role in the basal forebrain cholinergic sy stem. (C) 1997 Academic Press.