Institution: | aLaboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan bFuturistic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan cDepartment of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan dDepartment of Pathology, Surgery, and Taub Institute for Research on Alzheimer's Disease and the Ageing Brain, College of Physicians & Surgeons, Columbia University, 650 West 168th Street, New York, NY 10032, USA eDepartment of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan |
Abstract: | Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. Amyloid-β peptide (Aβ) has been proposed to be the primary cause of AD. In this study, we examined whether ovariectomy (OVX) could affect the levels of cofactors Aβ-binding alcohol dehydrogenase (ABAD) and receptor for advanced glycation endproducts (RAGE), which have been reported to potentiate Aβ-mediated neuronal perturbation, in mouse hippocampus, correlating with estrogen and Aβ 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 17β-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 Aβ1-40 level, although it significantly increased serum Aβ1-40 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 Aβ and hippocampal ABAD induced by ovarian hormone decline may be associated with pre-stage of memory deficit in postmenopausal women and Aβ-mediated AD pathology. |