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2017 年度 実施状況報告書

The underlying mechanisms of synaptic dysfunction after the irradiation

研究課題

研究課題/領域番号 17K16424
研究機関群馬大学

研究代表者

P Anggraeini  群馬大学, 未来先端研究機構, 助教 (60782050)

研究期間 (年度) 2017-04-01 – 2019-03-31
キーワードradiation / synaptic dysfunction / neurons / astrocytes / drebrin
研究実績の概要

Previously we have shown that radiation may produce acute temporary decreases of postsynaptic protein drebrin and no change in presynaptic protein synapsin I from the synapse. We hypothesized that the phenomenon of radiation-induced synaptic dysfunction has involvement of the astrocytes. It considers that X rays radiation may induce the release of gliotransmitter from the astrocytes and its bind to the receptor in neurons and cause the increase in calcium influx to the cells then affecting the massive decrease of drebrin along the dendrite. We aim to elucidate the possible mechanisms radiation-induced synaptic dysfunction and its prevention. By in vitro study, we irradiated neurons or astrocytes separately. The analyzing of synaptic proteins and receptors on neurons were made after 8 hours of incubation following the X- irradiation. We examine the synaptic function using synapsin I and drebrin immunoreactivity, and the involvement of NMDA receptors subunit NR1. Our results show there was the decrease in the number of drebrin and synapsin I cluster when radiation was given to the astrocytes or neurons alone, but the more significant decreased of drebrin was present when radiation was given to the neurons alone. Concurrent with the results, the immunoreactivity NMDA receptor subunit NR1 on neurons was increased 8 hours following radiation. These preliminary results showing that radiation to either neurons or astrocytes alone may have induced synaptic dysfunction and the involvement of NMDA receptor may play a significant role.

現在までの達成度 (区分)
現在までの達成度 (区分)

1: 当初の計画以上に進展している

理由

We have performed the in vivo study using mice for the NMDA antagonist experiment for prevention of radiation-induced decrease of drebrin. The results verified the involvement of NMDA receptor, which planned on the second year and performed by in vivo using mice, these results are smoother than the original plan.

今後の研究の推進方策

From the previous study shows that radiation-induced synaptic dysfunction has a significant role rather than the cells death. And our preliminary results indicate that the typical balance function between astrocytes and neurons has an essential part to cause dysfunction of the synapse which induced by X- irradiation. We will focus on how this radiation-induced synaptic dysfunction could happen and how to achieve the healthy balance between neurons and astrocytes as prevention and protection for synaptic function.

次年度使用額が生じた理由

Firstly we performed the irradiation on neurons and astrocytes separately, then analyze the synaptic proteins on neurons by Banker's method. Therefore we have not yet done High-throughput primary hippocampal culture method for examining the effects of radiation on neurons which may mediate by the conditioned medium from irradiated neurons on un-irradiated neurons, resulting in a remaining amount.

  • 研究成果

    (9件)

すべて 2018 2017

すべて 雑誌論文 (1件) (うち査読あり 1件、 オープンアクセス 1件) 学会発表 (8件) (うち国際学会 6件、 招待講演 1件)

  • [雑誌論文] N-methyl-D-aspartate Receptor Mediates X-irradiation-induced Drebrin Decrease in Hippocampus2018

    • 著者名/発表者名
      Shuchuan Miao, Noriko Koganezawa, Kenji Hanamura, Anggraeini Puspitasari, Tomoaki Shirao
    • 雑誌名

      The Kitakanto Medical Journal

      巻: Volume 68 Issue 2 ページ: 111-115

    • DOI

      https://doi.org/10.2974/kmj.68.111

    • 査読あり / オープンアクセス
  • [学会発表] X-irradiation of developing neurons causes delayed decrease in cell number and in synaptic related proteins of surviving neurons2018

    • 著者名/発表者名
      Anggraeini Puspitasari, Hiroyuki Yamazaki, Hidemasa Kawamura, Akihisa Takahashi, Yukari Yoshida, Tomoaki Shirao, Takashi Nakano, Kathryn D Held
    • 学会等名
      The 8th International Society of Radiation Neurobiology Conference, Tsukuba, Japan
    • 国際学会
  • [学会発表] X-irradiation on Immature Neurons (In Vitro) causes decreases of drebrin at mature stage2018

    • 著者名/発表者名
      Anggraeini Puspitasari, Hiroyuki Yamazaki, Takashi Nakano, Kathryn D Held, Tomoaki Shirao
    • 学会等名
      第95回日本生理学会大会、高松
  • [学会発表] Acute effects of low-LET and high-LET radiation on fear memory formation and its underlying mechanisms2017

    • 著者名/発表者名
      Anggraeini Puspitasari, Noriko Koganezawa, Tomoaki Shirao, Nobuhiko Kojima, Kathryn D Held, Akihisa Takahashi, Takashi Nakano
    • 学会等名
      The 5th International Symposium on Space Radiation and Particle Radiotherapy, including the 8th International Workshop on Space Research Radiation (IWSRR) Suzhou, China
    • 国際学会 / 招待講演
  • [学会発表] The effect of X-irradiation on neuronal function2017

    • 著者名/発表者名
      Anggraeini Puspitasari, Noriko Koganezawa, Hidemasa Kawamura, Hiroyuki Yamazaki, Akihisa Takahashi, Tomoaki Shirao, Takashi Nakano, Kathryn D Held
    • 学会等名
      The 23rd Annual Meeting of International Association for the sensitization of Cancer Treatment, in KARUIZAWA
    • 国際学会
  • [学会発表] Irradiation of immature neurons causes delayed decreases in the number of neurons and in the postsynaptic protein drebrin2017

    • 著者名/発表者名
      Anggraeini Puspitasari, Hidemasa Kawamura, Hiroyuki Yamazaki, Yukari Yoshida, Akihisa Takahashi, Tomoaki Shirao, Takashi Nakano, Kathryn D Held
    • 学会等名
      日本宇宙生物科学会31回大会, 前橋
  • [学会発表] In vivo and in vitro immunochemical assay for CNS synaptic dysfunction by X-irradiation2017

    • 著者名/発表者名
      Tomoaki Shirao, Anggraeini Puspitasari, Noriko Koganezawa, Hidemasa Kawamura, Akihisa Takahashi, Yuko Sekino, Takashi Nakano, Kathryn D Held
    • 学会等名
      2017 SPS Annual Meeting, Germany, Berlin.
    • 国際学会
  • [学会発表] Low Dose of X-irradiation on Immature Hippocampal Neurons (In Vitro) affecting number of neurons and drebrin clusters density2017

    • 著者名/発表者名
      Anggraeini Puspitasari, Akihisa Takahashi, Tomoaki Shirao, Takashi Nakano, Kathryn D Held.
    • 学会等名
      The 63rd annual International Meeting Radiation Research Society, Cancun, Mexico
    • 国際学会
  • [学会発表] Cell-cell communication may underlie radiation-induced synaptic dysfunction of mature neurons2017

    • 著者名/発表者名
      Anggraeini Puspitasari, Noriko Koganezawa, Kathryn D. Held, Tomoaki Shirao, Takashi Nakano
    • 学会等名
      Society for Neuroscience 2017, Washington, DC
    • 国際学会

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公開日: 2018-12-17  

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