title: Ovariectomy increases neuronal amyloid-beta binding alcohol dehydrogenase level in the mouse hippocampus.
abstract: Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. Amyloid-beta peptide (Abeta) has been proposed to be the primary cause of AD. In this study, we examined whether ovariectomy (OVX) could affect the levels of cofactors Abeta-binding alcohol dehydrogenase (ABAD) and receptor for advanced glycation endproducts (RAGE), which have been reported to potentiate Abeta-mediated neuronal perturbation, in mouse hippocampus, correlating with estrogen and Abeta levels. Female ICR mice were randomly divided into ovariectomized or sham-operated groups, and biochemical analyses were carried out at 5 weeks after the operation. OVX for 5 weeks significantly decreased hippocampal 17beta-estradiol level, while it tended to reduce the hormone level in serum, compared with the sham-operated control. In contrast, OVX did not affect hippocampal Abeta(1-40) level, although it significantly increased serum Abeta(1-40) level. Furthermore, we demonstrated that OVX increased hippocampal ABAD level in neurons, but not astrocytes, while it did not affect RAGE level. These findings suggest that the expression of neuronal ABAD depends on estrogen level in the hippocampus and the increase in serum Abeta and hippocampal ABAD induced by ovarian hormone decline may be associated with pre-stage of memory deficit in postmenopausal women and Abeta-mediated AD pathology.
authors.affiliation: Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Fukuzaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Yoko
authors.initials: Y
authors.lastname: Funatsu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Himeno
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitahara
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ibi
authors.forename: Koji
authors.initials: K
authors.lastname: Koike
authors.forename: Masaki
authors.initials: M
authors.lastname: Inoue
authors.forename: Shi Du
authors.initials: SD
authors.lastname: Yan
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D004268:DNA-Binding Proteins; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010052:Ovariectomy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D004958:Estradiol; D000426:Alcohol Dehydrogenase