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青春期におけるストレス誘発によるドーパミナージックニューロンの表遺伝子制御は,グルココルチコイドを介して行われます
Minae Niwa1, Hanna Jaaro-Peled, Stephanie Tankou
1Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.
まとめ
青春期のストレスと遺伝的リスクは,脳の表遺伝的変化を誘発し,精神病的なうつ病のような成人神経精神疾患につながる可能性があります. グルココルチコイドは,このリンクを媒介し,ドーパミンニューロン機能に影響を与えます.
科学分野:
- 神経科学は神経科学である.
- 分子精神医学は分子精神医学である.
- 発達心理学の心理学について
背景:
- 幼児期と青春期の環境ストレス要因は,脳の発達と成人時の行動に影響を及ぼします.
- 過剰なストレスは,成人発症神経精神疾患につながる可能性があります.
- グルココルチコイドは,ストレスと表遺伝的変化の関連付けに関与しています.
研究 の 目的:
- グルココルチコイドの媒介による青春期のストレス要因が,神経細胞における表遺伝子制御に影響を与えるメカニズムを解明する.
- ドーパミナージック系におけるストレス,遺伝,および表遺伝的変異の関連性を調査する.
- マウスモデルを使用して精神病的なうつ病をモデル化します.
主な方法:
- 軽度の隔離ストレスを受けたマウスモデルを使用しました.
- ドーパミナージックニューロンにおけるチロシンヒドロキシラーゼ遺伝子のDNAハイパーメチル化などのエピジェネティック改変を調べた.
- 神経化学的および行動的欠陥を評価した.
- グルココルチコイド受容体アンタゴニストを投与した.
主要な成果:
- 遺伝的リスクと組み合わせた軽度の隔離ストレスは,中皮質のドーパミン反応性ニューロンにおけるチロシンヒドロキシラーゼ遺伝子のDNAハイパーメチル化を誘発した.
- これらの分子変化は,神経化学的および行動的欠陥と相関していた.
- 観察された欠乏症と分子変化は,グルココルチコイド受容体対抗剤によって逆転した.
結論:
- グルココルチコイドは,青春期のストレスとドーパミナージックニューロンの表遺伝的変化を結びつける上で重要な役割を果たします.
- このメカニズムは,ストレス,グルココルチコイド,エピジェネティクスを含み,精神病性うつ病などの神経精神疾患の発症に寄与する.
- マウスモデルは,精神病性うつ病の重要な生物学的および現象的側面を効果的に複製しています.
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