Placental Extract Improves Hippocampal Neuronal Loss and Fear Memory Impairment Resulting From Chronic Restraint Stress in Ovariectomized Mice

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  • Takuma Kazuhiro
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
  • Mizoguchi Hiroyuki
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Japan
  • Funatsu Yoko
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan
  • Kitahara Yuko
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan
  • Ibi Daisuke
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan
  • Kamei Hiroyuki
    Laboratory of Clinical Pharmacy Practice and Health Care Management, Faculty of Pharmacy, Meijo University, Japan Laboratory of Clinical Pharmacy Practice and Health Care Management, Faculty of Pharmacy, Meijo University, Japan
  • Matsuda Toshio
    Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
  • Koike Koji
    Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Japan Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Japan
  • Inoue Masaki
    Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Japan Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Japan
  • Nagai Taku
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan
  • Yamada Kiyofumi
    Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan CREST, JST, Japan Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan CREST, JST, Japan

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We have recently found that combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and mice and that estrogen replacement and chronic treatment with Ginkgo biloba extract EGb 761 suppress the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of placental extract on the memory impairment and neuromorphological change in OVX/stress-subjected mice. Female Slc:ICR strain mice were randomly divided into four groups: vehicle-treated OVX, porcine placental extract (120 and 2160 mg/kg)-treated OVX, and sham-operated control groups. Two weeks after surgical operation, OVX mice underwent restraint stress for 21 days (6 h/day), and all animals were then subjected to a contextual fear conditioning test followed by morphological examination by Nissl staining. Placental extract was orally administered once daily until the behavioral analysis was carried out. Chronic treatment with both doses of placental extract improved the OVX/stress-induced fear memory impairment and Nissl-positive cell loss of the hippocampal CA3 region, although it did not affect the loss of bone mineral density and increase in body weight after OVX. These results have important implications for the neuroprotective and cognition-enhancing effects of placental extract in postmenopausal women.

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