Ovariectomy combined with amyloid ß1-42 impairs memory by decreasing acetylcholine release and ?7nAChR expression without induction of apoptosis in the hippocampus CA1 neurons of rats

Abstract

In this study, the effect of ovariectomy and amyloid P1-42 (Aß1-42)on eight-armed radial maze performance, acetylcholine (ACh) release, ?7nACh receptor (?7nAChR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, and apoptosis of CA1 neurons in the dorsal hippocampus were investigated in rat. The results showed that the dorsal hippocampus of sham rats contains 136.7 ± 16.7 to 160.4 ± 21.1 fmol/µl ACh, and respective 201 ± 22.9 and 416.6 ± 66.3 expression of mRNA for ?7nAChR and GAPDH. Ovariectomy alone, after 4 weeks, did not impair memory, and neither induced apoptosis nor changed the basal ACh release. On the other hand, Aß1-42 (600 pmol/10 µl/ body/day i.c.v. for 7 days) impaired memory, an effect characterized by increased error choices and reduced (50-59%) ACh release, but only with slight apoptosis. Moreover, ovariectomy combined with Aß1-42 induced memory impairment characterized by decreased numbers of correct choices and increased numbers of errors. This effect was accompanied by a decrease of the basal ACh level (67%), ?7nAChR mRNA expression (52%) and ?7nAChR/GAPDH ratio (44%) without induction of apoptosis in the dorsal hippocampus. The high K+-evoked ACh release was not altered in ovariectomized rats, but was decreased by Aß1-42 (43%) and ovariectomy + Aß1-42 (80%). These results suggest that ovariectomy-induced hormonal deprivation after 4 weeks, when accompanied by Aß1-42 accumulation in the dorsal hippocampus, could impair memory by decreasing ACh release and ?7nAChR expression without inducing apoptosis in the CA1 field of the dorsal hippocampus. © Springer 2004.