横部ヘブンヌラのアストログリアルキル4.1は,うつ病におけるニューロン爆発を誘発する

Yihui Cui^1,2, Yan Yang^1,2, Zheyi Ni¹

¹Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310058, China.

Nature

|February 16, 2018

まとめ

LHbのニューロンの爆発が増加すると,うつ病が起こります. 研究者らは,アストログリアルカリウムチャネルKir4.1がLHbで上位に調節され,アストログリアル機能とうつ病のような行動が結びついていることを発見しました.

科学分野:

神経科学
細胞生物学
精神科

背景:

側頭葉 (LHb) のニューロンの爆発は,うつ病のような行動と関連しています.
うつ病におけるこの神経活動の増加の根本的な原因は不明である.

研究の目的:

鬱病のモデルでLHbニューロン活性を増強する分子メカニズムを調査する.
LHb ニューロンの機能を調節する Glial 細胞,特に astrocytes の役割を調査する.

主な方法:

LHbで差異的に発現するタンパク質を特定するための高通量タンパク質スクリーニング.
電気生理学的記録とニューロン活動と膠質機能の評価のための計算モデル
ネズミのモデルにおけるアストロサイト特有のKir4.1発現の遺伝子操作.

主要な成果:

鬱病モデルのLHbでは,アストログリアルカリウムチャネルKir4. 1のアップレギュレーションが確認された.
アストロサイトにおけるKir4. 1発現は,LHbニューロン膜の潜在性と爆発活動を緊密に調節する.
アストロサイトでKir4.1を調節すると双方向的にニューロンの爆発とうつ病のような症状が変化します

結論:

アストログリアルKir4. 1は,LHbニューロンの発火モードを調節する上で重要な役割を果たします.
精神疾患の病理生理学には,ペリスオマティック空間におけるグリア-ニューロンの相互作用が関与している.
LHbのKir4. 1は,臨床的うつ病の潜在的な治療目標を表しています.

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