Ovariectomy combined with amyloid β_1-42 impairs memory by decreasing acetylcholine release and α7nAChR expression without induction of apoptosis in the hippocampus CA1 neurons of rats

In this study, the effect of ovariectomy and amyloid P_1-42 (Aβ_1-42)on eight-armed radial maze performance, acetylcholine (ACh) release, α7nACh receptor (α7nAChR), 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 α7nAChR 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, Aβ_1-42 (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 Aβ_1-42 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%), α7nAChR mRNA expression (52%) and α7nAChR/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 Aβ_1-42 (43%) and ovariectomy + Aβ_1-42 (80%). These results suggest that ovariectomy-induced hormonal deprivation after 4 weeks, when accompanied by Aβ_1-42 accumulation in the dorsal hippocampus, could impair memory by decreasing ACh release and α7nAChR expression without inducing apoptosis in the CA1 field of the dorsal hippocampus.