Ovariectomy increases neuronal amyloid-beta binding alcohol dehydrogenase level in the mouse hippocampus.
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.
Fukuzaki
Emiko
E
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Japan.
Takuma
Kazuhiro
K
Funatsu
Yoko
Y
Himeno
Yukiko
Y
Kitahara
Yuko
Y
Gu
Bin
B
Mizoguchi
Hiroyuki
H
Ibi
Daisuke
D
Koike
Koji
K
Inoue
Masaki
M
Yan
Shi Du
SD
Yamada
Kiyofumi
K
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
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