title: Ovariectomy combined with amyloid beta(1-42) impairs memory by decreasing acetylcholine release and alpha 7nAChR expression without induction of apoptosis in the hippocampus CA1 neurons of rats.
abstract: In this study, the effect of ovariectomy and amyloid Beta(1-42) (ABeta(1-42))on eight-armed radial maze performance, acetylcholine (ACh) release, Alpha7nACh receptor (Alpha7nAChr), 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/microl ACh, and respective 201 -/+ 22.9 and 416.6 -/+ 66.3 expression of mRNA for a7nAChR 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, ABeta(1-42) (600 pmol/10 microl/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 ABeta(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%), a7nAChR mRNA expression (52%) and a7nAChR/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 ABeta(1-42) (43%) and ovariectomy + ABeta(1-42) (80%). These results suggest that ovariectomy-induced hormonal deprivation after 4 weeks, when accompanied by ABeta(1-42) accumulation in the dorsal hippocampus, could impair memory by decreasing ACh release and a7nAChR expression without inducing apoptosis in the CA1 field of the dorsal hippocampus.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. iwasakik@fukuoka-u.ac.jp
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Izzettin
authors.initials: I
authors.lastname: Hatip-Al-Khatib
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Yuki
authors.initials: Y
authors.lastname: Akiyoshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takagaki
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Inui
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D016229:Amyloid beta-Peptides; C579165:Chrna7 protein, rat; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C075222:amyloid beta-protein (1-42); D000109:Acetylcholine