Long-term deprivation of oestrogens by ovariectomy potentiates β-amyloid-induced working memory deficits in rats

Authors

  • Kiyofumi Yamada,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Tomoko Tanaka,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
    2. Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Tenpaku-ku, Nagoya 468-0077, Japan
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  • Li-Bo Zou,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Kouji Senzaki,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Kohji Yano,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Takashi Osada,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Olariu Ana,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Xiuhai Ren,

    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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  • Tsutomu Kameyama,

    1. Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Tenpaku-ku, Nagoya 468-0077, Japan
    2. Japan Institute of Psychopharmacology, Higashi-ku, Nagoya 461-8508, Japan
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  • Toshitaka Nabeshima

    Corresponding author
    1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
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Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan. E-mail: tnabeshi@tsuru.med.nagoya-u.ac.jp

Abstract

  • In the present study, we examined whether deprivation of oestrogens by ovariectomy could modify learning and memory deficits caused by a continuous intracerebroventricular (i.c.v.) infusion of amyloid β-peptide (Aβ), the major constituent of senile plaques in AD.

  • Neither long-term (3 months) nor short-term (1 month), deprivation of oestrogens by ovariectomy caused a significant impairment in spatial learning and memory in a water maze and spontaneous alternation behaviour in a Y-maze.

  • A continuous i.c.v. infusion of Aβ-(1-42) caused spatial learning and memory deficits in both ovariectomized and sham-operated rats.

  • The Aβ-induced working memory deficits were significantly potentiated in ovariectomized rats compared with sham-operated rats when mnemonic ability was examined 3 months after ovariectomy.

  • These results suggest that long-term deprivation of oestrogens induced by ovariectomy increases susceptibility to memory deficits produced by Aβ-(1-42) in rats.

British Journal of Pharmacology (1999) 128, 419–427; doi:10.1038/sj.bjp.0702811

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