2017 Fiscal Year Research-status Report
The underlying mechanisms of synaptic dysfunction after the irradiation
| Project/Area Number |
17K16424
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| Research Institution | Gunma University |
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Principal Investigator |
P Anggraeini 群馬大学, 未来先端研究機構, 助教 (60782050)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | radiation / synaptic dysfunction / neurons / astrocytes / drebrin |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
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.
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| Strategy for Future Research Activity |
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.
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| Causes of Carryover |
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.
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Research Products
(9 results)
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[Presentation] The effect of X-irradiation on neuronal function2017
Author(s)
Anggraeini Puspitasari, Noriko Koganezawa, Hidemasa Kawamura, Hiroyuki Yamazaki, Akihisa Takahashi, Tomoaki Shirao, Takashi Nakano, Kathryn D Held
Organizer
The 23rd Annual Meeting of International Association for the sensitization of Cancer Treatment, in KARUIZAWA
Int'l Joint Research
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