認知、ストレス感知における海馬亜鉛のユニークな応答とストレス性精神障害の予防

2010 年度 研究成果報告書

• 研究課題/領域番号: 19390035
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 環境系薬学
• 研究機関: 静岡県立大学
• 研究代表者: 武田 厚司 静岡県立大学, 薬学部, 准教授 (90145714)
• 研究期間 (年度): 2007 – 2010
• キーワード: 亜鉛 / 海馬 / 学習 / 記憶 / シナプス可塑性 / 長期増強 / ストレス / 精神障害

研究概要

長期増強(ong-term potentiation : LTP)などのシナプス可塑性は学習・記憶の分子基盤と考えられている。記憶形成に関係する海馬において、苔状線維-CA3錐体細胞間でのLTPは亜鉛イオンにより減弱され、シャーファー側肢-CA1錐体細胞間でのLTPは亜鉛イオンにより増強されることを明らかにした。一方、ストレス負荷によりシナプス可塑性や学習・記憶は影響を受けるが、ラットに急性ストレスを負荷すると海馬細胞外(シナプス)亜鉛ホメオスタシスが変化し、LTP発現が減弱することを明らかにした。以上より、海馬での亜鉛シグナリングがLTPの調節に深く関与することが示唆された。

研究成果

• [雑誌論文] Zinc Differentially Acts on Components of Long-term Potentiation at Hippocampal CA1 Synapse. (2010)
  • 著者名/発表者名: Atsushi Takeda, Haruka Iwaki, Masaki Ando, Kosuke Itagaki, Miki Suzuki, Naoto Oku
  • 雑誌名: Brain Res. 1323 ページ: 59-64
  • 査読あり
• [雑誌論文] Susceptibility to Stress in Young Rats after 2-week Zinc Deprivation. (2010)
  • 著者名/発表者名: Mitsugu Watanabe, Haruna Tamano, Toshinori Kikuchi, Atsushi Takeda
  • 雑誌名: Neurochem. Int. 56 ページ: 410-416
  • 査読あり
• [雑誌論文] Synephrine, a Component of Evodiae Fructus, Constricts Isolated Rat Aorta via Adrenergic and Serotonergic Receptors. (2009)
  • 著者名/発表者名: Tomoko Hibino, Mitsutoshi Yuzurihara, Yoshio Kasa, Atsushi Takeda
  • 雑誌名: J. Pharmacol. Sci. 111 ページ: 73-81
  • 査読あり
• [雑誌論文] Decreased brain zinc availability reduces hippocampal neurogenesis in mice and rats. (2009)
  • 著者名/発表者名: Sang Won Suh, Seok Joon Won, Aaron M. Hamby, Yang Fan, Christian T. Sheline, Haruna Tamano, Atsushi Takeda, Jialing Liu
  • 雑誌名: J. Cereb. Blood Flow Metab. 29 ページ: 1579-1588
  • 査読あり
• [雑誌論文] Unique response of zinc in the hippocampus to behavioral stress and attenuation of subsequent mossy fiber long-term potentiation. (2009)
  • 著者名/発表者名: Atsushi Takeda, Masaki Ando, Shingo Kanno, Naoto Oku
  • 雑誌名: NeuroToxicology 30 ページ: 712-717
  • 査読あり
• [雑誌論文] Behavior in the forced swim test and neurochemical changes in the hippocampus in young rats after 2-week zinc deprivation. (2009)
  • 著者名/発表者名: Haruna Tamano, Fumika Kan, Mika Kawamura, Naoto Oku, Atsushi Takeda
  • 雑誌名: Neurochem. Int. 55 ページ: 536-541
  • 査読あり
• [雑誌論文] Facilitation of zinc influx via AMPA/kainate receptor activation in the hippocampus. (2009)
  • 著者名/発表者名: Atsushi Takeda, Naomi Sakurada, Masaki Ando, Shingo Kanno, Naoto Oku
  • 雑誌名: Neurochem. Int. 55 ページ: 376-382
  • 査読あり
• [雑誌論文] High K+-induced increase in extracellular glutamate in zinc deficiency and endogenous zinc action. (2009)
  • 著者名/発表者名: Atsushi Takeda, Hiromasa Itoh, Haruna Tamano, Naoto Oku
  • 雑誌名: J. Health Sci. 55 ページ: 405-412
  • 査読あり
• [雑誌論文] Goshuyuto, a Japanese traditional medicine, and aqueous extracts of Evodiae Fructus constrict isolated rat aorta via adrenergic and/or serotonergic receptors. (2009)
  • 著者名/発表者名: Tomoko Hibino, Mitsutoshi Yuzurihara, Hitomi Kanno, Yoshio Kasa, Atsushi Takeda
  • 雑誌名: Biol. Pharm. Bull. 32 ページ: 237-241
  • 査読あり
• [雑誌論文] Positive Modulation of Long-term Potentiation at Hippocampal CA1 Synapses by Low Micromolar Concentrations of Zinc. (2009)
  • 著者名/発表者名: Atsushi Takeda, Sayuri Fuke, Masaki Ando, Naoto Oku
  • 雑誌名: Neuroscience 158 ページ: 585-591
  • 査読あり
• [雑誌論文] Abnormal calcium mobilization in hippocampal slices of epileptic animals fed a zinc-deficient diet. (2009)
  • 著者名/発表者名: Atsushi Takeda, Hiromasa Itoh, Akito Nagayoshi, Naoto Oku
  • 雑誌名: Epilepsy Res. 83 ページ: 73-80
  • 査読あり
• [雑誌論文] Goshuyuto, a traditional Japanese medicine for migraine, inhibits platelet aggregation in guinea-pig whole blood. (2008)
  • 著者名/発表者名: Tomoko Hibino, Mitsutoshi Yuzurihara, Kiyoshi Terawaki, Hitomi Kanno, Yoshio Kasa, Atsushi Takeda
  • 雑誌名: J. Pharmacol. Sci. 108 ページ: 89-94
  • 査読あり
• [雑誌論文] Attenuation of abnormal glutamate release in zinc deficiency by zinc and Yokukansan. (2008)
  • 著者名/発表者名: Atsushi Takeda, Haruna Tamano, Hiromasa Itoh, Naoto Oku
  • 雑誌名: Neurochem. Int. 53 ページ: 230-235
  • 査読あり
• [雑誌論文] Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc. (2008)
  • 著者名/発表者名: Atsushi Takeda, Shingo Kanno, Naomi Sakurada, Masaki Ando, Naoto Oku
  • 雑誌名: J. Neurosci. Res. 86 ページ: 2909-2911
  • 査読あり
• [雑誌論文] Enhancement of social isolation-induced aggressive behavior of young mice by zinc deficiency. (2008)
  • 著者名/発表者名: Atsushi Takeda, Haruna Tamano, Fumika Kan, Tomoyuki Hanajima, Kohei Yamada, Naoto Oku
  • 雑誌名: Life Sci. 82 ページ: 909-914
  • 査読あり
• [雑誌論文] Suppressive effect of Yokukansan on excessive release of glutamate and aspartate in the hippocampus of zinc-deficient rats. (2008)
  • 著者名/発表者名: Atsushi Takeda, Hiromasa Itoh, Haruna Tamano, Mitsutoshi Yuzurihara, Naoto Oku
  • 雑誌名: Nutr. Neurosci. 11 ページ: 41-46
  • 査読あり
• [雑誌論文] Enhanced basal activity of hippocampal mossy fibers in zinc deficiency. (2008)
  • 著者名/発表者名: Atsushi Takeda, Hiromasa Itoh, Kohei Yamada, Haruna Tamano, Naoto Oku
  • 雑誌名: BioMetals 21 ページ: 545-552
  • 査読あり
• [雑誌論文] Vulnerability to seizures induced by potassium dyshomeostasis in the hippocampus in aged rats. (2008)
  • 著者名/発表者名: Atsushi Takeda, Naomi Sakurada, Shingo Kanno, Masaki Ando, Naoto Oku
  • 雑誌名: J. Health Sci. 54 ページ: 37-42
  • 査読あり
• [雑誌論文] Hippocampal calcium dyshomeostasis and long-term potentiation in 2-week zinc deficiency. (2008)
  • 著者名/発表者名: Atsushi Takeda, Kohei Yamada, Haruna Tamano, Sayuri Fuke, Mika Kawamura, Naoto Oku
  • 雑誌名: Neurochem. Int. 52 ページ: 241-246
  • 査読あり
• [雑誌論文] Negative modulation of presynaptic activity by zinc released from Schaffer collaterals. (2007)
  • 著者名/発表者名: Atsushi Takeda, Sayuri Fuke, Wataru Tsutsumi, Naoto Oku
  • 雑誌名: J. Neurosci. Res. 85 ページ: 3666-3672
  • 査読あり
• [雑誌論文] Role of zinc influx via AMPA/kainate receptor activation in metabotropic glutamate receptor-mediated calcium release. (2007)
  • 著者名/発表者名: Atsushi Takeda, Sayuri Fuke, Akira Minami, Naoto Oku
  • 雑誌名: J. Neurosci. Res. 85 ページ: 1310-1317
  • 査読あり
• [雑誌論文] Anxiety-like behavior of young rats after 2-week zinc deprivation. (2007)
  • 著者名/発表者名: Atsushi Takeda, Haruna Tamano, Fumika Kan, Hiromasa Itoh, Naoto Oku
  • 雑誌名: Behav. Brain Res. 177 ページ: 1-6
  • 査読あり
• [雑誌論文] Response of hippocampal mossy fiber zinc to excessive glutamate release. (2007)
  • 著者名/発表者名: Atsushi Takeda, Akira Minami, Naomi Sakurada, Satoko Nakajima, Naoto Oku
  • 雑誌名: Neurochem. Int. 50 ページ: 322-327
  • 査読あり
• [雑誌論文] Increases in Extracellular Zinc in the Amygdala in Acquisition and Recall of Fear Experience and their Roles in Response to Fear.
  • 著者名/発表者名: Atsushi Takeda, Haruna Tamano, Sachie Imano, Naoto Oku
  • 雑誌名: Neuroscience (in press)
  • 査読あり
• [学会発表] Protective effect of theanine on attenuation of long-term potentiation at hippocampal CA1 synapses after acute behavioral stress. (2009)
  • 著者名/発表者名: Miki Suzuki, Atsushi Takeda, Haruna Tamano, Naoto Oku, Kazuhiro Sakamoto, Naoto Inui, Hidehiko Yokogoshi
  • 学会等名: The 2nd International Conference on Health and Longevity Sciences
  • 発表場所: Shizuoka, Japan
  • 年月日: 2009-10-01
• [学会発表] Attenuation of mossy fiber long-term potentiation by acute behavioral stress and effects of zinc and theanine. (2008)
  • 著者名/発表者名: Atsushi Takeda, Hidehiko Yokogoshi, Naoto Oku
  • 学会等名: 1st International Conference on Health and Longevity Sciences
  • 発表場所: Shizuoka, Japan
  • 年月日: 2008-12-18
• [学会発表] Region-dependent Responses of Extracelluar Zinc in the Hippocampus to Acute Behavioral Stress. (2008)
  • 著者名/発表者名: Atsushi Takeda, Masaki Ando, Shingo Kanno, Naomi Sakurada, Naoto Oku
  • 学会等名: Society for Neuroscience 38th Annual Meeting
  • 発表場所: Washington, DC, USA
  • 年月日: 2008-11-16
• [学会発表] Attenuation of Hippocampal Mossy Fiber Long-term Potentiation by Low Micromolar Concentrations of Zinc. (2008)
  • 著者名/発表者名: Masaki Ando, Atsushi Takeda, Shingo Kanno, Naomi Sakurada, Naoto Oku
  • 学会等名: Society for Neuroscience 38th Annual Meeting
  • 発表場所: Washington, DC, USA
  • 年月日: 2008-11-15
• [学会発表] Increase in depression-like behavior and hippocampal dysfunction in zinc-deficient rats via glucocorticoid hypersecretion. (2008)
  • 著者名/発表者名: Haruna Tamano, Atsushi Takeda, Mika Kawamura, Naoto Oku
  • 学会等名: Society for Neuroscience 38th Annual Meeting
  • 発表場所: Washington, DC, USA
  • 年月日: 2008-11-15
• [学会発表] Involvement of Enhanced Mossy Fiber Exocytosis in Seizure Susceptibility in Zinc Deficiency. (2008)
  • 著者名/発表者名: Hiromasa Itoh, Atsushi Takeda, Naoto Oku
  • 学会等名: Society for Zinc Biology Meeting
  • 発表場所: Banff, Canada
  • 年月日: 2008-02-13
• [学会発表] Enhancement of aggressive behavior of young mice induced with social isolation in zinc deficiency. (2007)
  • 著者名/発表者名: Haruna Tamano, Fumika Kan, Atsushi Takeda, Naoto Oku
  • 学会等名: A Joint Conference on Trace Elements in Diet, Nutrition, & Health: Essentiality and Toxicity
  • 発表場所: Crete, Greece
  • 年月日: 2007-10-25
• [学会発表] Involvement of zinc in synaptic plasticity and neurodegeneration in the hippocampus via crosstalk with calcium. (2007)
  • 著者名/発表者名: Atsushi Takeda, Sayuri Fuke, Naomi Sakurada, Akira Minami, Naoto Oku
  • 学会等名: A Joint Conference on Trace Elements in Diet, Nutrition, & Health: Essentiality and Toxicity
  • 発表場所: Crete, Greece
  • 年月日: 2007-10-25
• [学会発表] Unique Response of Extracelluar Zinc in the Ventral Hippocampus against Novelty Stress. (2007)
  • 著者名/発表者名: Shingo Kanno, Naomi Sakurada, Akira Minami, Atsushi Takeda, Naoto Oku
  • 学会等名: A Joint Conference on Trace Elements in Diet, Nutrition, & Health: Essentiality and Toxicity
  • 発表場所: Crete, Greece
  • 年月日: 2007-10-25
• [学会発表] Increase in depression-like behavior of young rats in zinc deficiency. (2007)
  • 著者名/発表者名: Mika Kawamura, Haruna Tamano, Hiromasa Itoh, Atsushi Takeda, Naoto Oku
  • 学会等名: A Joint Conference on Trace Elements in Diet, Nutrition, & Health: Essentiality and Toxicity
  • 発表場所: Crete, Greece
  • 年月日: 2007-10-25
• [学会発表] Preferential dysfunction in the hippocampus in zinc deficiency. (2007)
  • 著者名/発表者名: Fumika Kan, Haruna Tamano, Hiromasa Itoh, Atsushi Takeda, Naoto Oku
  • 学会等名: A Joint Conference on Trace Elements in Diet, Nutrition, & Health: Essentiality and Toxicity
  • 発表場所: Crete, Greece
  • 年月日: 2007-10-25