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Functional involvement of P/Q-type calcium channel in synapse elimination in adult brains

P/Q 型钙通道在成人大脑突触消除中的功能参与

基本信息

批准号：
21H02589
负责人：
渡辺雅彦
金额：
$ 11.15万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2021
资助国家：
日本
起止时间：
2021-04-01 至 2025-03-31
项目状态：
未结题

项目摘要

令和3年度の研究活動において、新潟大学脳研究所の崎村建司名誉教授らが開発したP/Q型VDCC のチャネル本体をコードするCav2.1遺伝子のfloxマウスと、プロゲステロン誘導剤（RU-486）依存的に活性化するCreリコンビナーゼをプルキンエ細胞選択的に発現するGluD2-CrePRマウスを入手し、成体期におけるプロゲステロン誘導剤投与によりてCav2.1遺伝子をプルキンエ細胞のみに選択的に欠損させるモデルマウスが完成したことを確認した。令和4年の研究活動では、このモデルを用いて、成体期遺伝子欠損に伴う小脳の組織学的変化を光学顕微鏡と電子顕微鏡を用いて解析した。その結果、薬剤投与後1週目よりCav2.1タンパク質の発現量が、前葉・後葉を問わず小脳全体で減少していた。プルキンエ細胞の細胞死は前葉では投与後3週目より、後葉では5週目より発生していた。また、投与後3週目より分子そうの厚さが減少し、5週目より近位樹状突起における異所性スパインの増加が認められた。これら細胞死や異所性スパインの増加は電子顕微鏡でも確認された。以上の表現型は、受精卵の段階から遺伝子を欠損する完全欠失型ノックアウトマウスの表現型とも一致しており、Cav2.1は成体期においても、細胞死を抑止し近位樹状突起におけるスパイン形成を抑制する機能、すなわち近位樹状突起におけるシナプス刈り込みの促進する機能、を果たしていることが明らかとなった。今後は、これらの研究成果を基盤として、当初の研究計画に従って、平行線維支配テリトリーと登上線維支配テリトリーの分離に関する解析（渡辺、宮崎）に取り組む。

In 2003, Honorary Professor Kawasaki, Honorary Professor, Department of Research, Institute of Research and Development, Niigata University, opened a series of experiments on the implementation of the PQ-type VDCC platform, the Cav2.1 subsystem, the flox cluster, the RU-486-dependent Cre cycle, and the candidate cell selection program for the current GluD2-CrePR cycle. When you are an adult, you need to make sure that you do not know what to do when you are an adult. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are an adult, you do not know what to do. When you are Ling and 4-year-old research activities, research programs, and adult studies are not available in the laboratory. The chemical optical micro-electronic micrometer is used to analyze the microelectronics. The result of the experiment, the result of the test, the result, the result and the result. Before the death of the cell, it was cast before the death of the cell, and then it was cast in the back of 3 eyes and 5 eyes. In the last 3 eyes, the molecules are thicker and thicker, and the proximal protuberances of 5 eyes are thicker, thicker, thicker and thicker. Please add the computer microphone to make sure that the phone is dead. The above phenotype, the zygote segment of the zygote, the leg of the zygote, the complete loss of the zygote, the concordance of the Cav2.1, the adult stage of the zygote, the inhibition of the proximal protuberance, the inhibition of the formation of the mechanism, the proximal protuberance of the zygote, the proximal protuberance of the zygote, the clipping of the zygote, the promotion of the mechanism, the promotion of the mechanism, the inhibition of the formation of the proximal protuberance I don't know if I know what's going on. In the future, the results of the research are based on the results of the research, the original research project, the parallel control system, and the data analysis (ferry, Kawasaki).