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.
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.
Iwasaki
Katsunori
K
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. iwasakik@fukuoka-u.ac.jp
Hatip-Al-Khatib
Izzettin
I
Egashira
Nobuaki
N
Akiyoshi
Yuki
Y
Arai
Takashi
T
Mishima
Kenichi
K
Takagaki
Yuki
Y
Inui
Keiichiro
K
Fujiwara
Michihiro
M
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
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