統合失調症モデルの聴覚皮質へのタラミックインプットの特定の障害
Sungkun Chun1, Joby J Westmoreland1, Ildar T Bayazitov1
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Science (New York, N.Y.)
|June 7, 2014
まとめ
統合失調症 統合失調症 統合失調症
科学分野:
- 神経科学は神経科学である.
- 遺伝学 遺伝学とは
- 薬理学 薬理学とは
背景:
- 統合失調症における聴覚幻覚は,D2ドーパミン受容体 (Drd2s) を標的とする抗精神病薬によって治療されます.
- 統合失調症における抗精神病薬に対する感受性の根底にある神経機構は不明である.
- 統合失調症に関連した22q11消去症候群 (22q11DS) は,これらの欠陥を研究するためのモデルを提供します.
研究 の 目的:
- 22q11DS.DS.のネズミモデルにおける神経回路の障害を調査する.
- 統合失調症に関連した精神病における抗精神病薬感受性のメカニズムを特定する.
- 甲状腺皮質経路の機能不全におけるDgcr8とmicroRNAの役割を明らかにする.
主な方法:
- 22q11DS.DS.のネズミモデルを使用した.
- サナプス伝達がthalamocorticalのグルタマタージックプロジェクションで検証された.
- 評価されたDrd2レベルと,タラムスと聴覚皮質におけるマイクロRNA処理.
- 測定された音響の衝撃反応.
主要な成果:
- 22q11DSマウスにおける聴覚性タラモコルチカルプロジェクションにおける突発性シナプス伝送の障害を特定した.
- 22q11DSマウスのタラムスのDrd2レベルが上昇し,抗精神病薬に対する感受性が高まった.
- Dgcr8のハプロイン欠乏がDrd2の上昇と過敏症を引き起こすことが実証されました.
- 22q11DSマウスの音響性ショック反応が欠乏していることが観察されました.
結論:
- Dgcr8-microRNA経路の障害により,Drd2が上昇し,thalamocortical機能が異常する.
- このタラモ皮質の障害は,統合失調症に関連した精神病における重要な病原性メカニズムである.
- 発見は,統合失調症における聴覚幻覚のための新しい治療目標を示唆しています.
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