関連する実験動画
トラウマ後ストレス障害はPACAPとPAC1受容体に関連しています
Kerry J Ressler1, Kristina B Mercer, Bekh Bradley
1Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. kressle@emory.edu
Nature
|February 26, 2011
まとめ
下垂体アデニラートサイクラゼ活性化ポリペプチド (PACAP) 経路が,外傷後ストレス障害 (PTSD) に関与することは,性別に特異的です. 低いPACAPレベルと特定の遺伝子変異は,女性のPTSD症状と関連しており,潜在的なバイオマーカーを示唆しています.
科学分野:
- 神経生物学 神経生物学とは
- 遺伝学 遺伝学とは
- 精神科医は精神病を患っている.
背景:
- pituitary adenylate cyclase-activating polypeptide (PACAP) は,細胞のストレス反応を大きく調節している.
- 人間の心理的ストレス,特にトラウマ後ストレス障害 (PTSD) に関するPACAP-PAC1受容体の経路の役割は不明である.
研究 の 目的:
- 性別特異的な効果に焦点を当てて,PACAP-PAC1経路とPTSDの関連性を調査する.
- PACAP経路内でPTSDの潜在的な遺伝子および分子バイオマーカーを特定する.
主な方法:
- PTSDの診断と症状に関連して,ADCYAP1とADCYAP1R1遺伝子の44の単一のヌクレオチドポリモルフィズム (SNP) を調べました.
- PACAPの血中濃度,恐怖の生理学,およびヒトのADCYAP1R1 mRNA発現を評価した.
- 恐怖条件付けとエストロゲン置換の下でADCYAP1R1 mRNA誘導を研究するために,ネズミのモデルを使用しました.
主要な成果:
- PACAPの血中濃度と女性におけるPTSDとの間に,性別の関連性が見られた.
- ADCYAP1R1の特定のSNP (rs2267735) は,PTSDの診断と女性のみの症状と有意に関連していました.
- このSNPは,人間の脳における恐怖の差別とADCYAP1R1 mRNA発現と相関しており,ADCYAP1R1メチル化はPTSDに関連していた.
- ネズミの研究では,ADCYAP1R1 mRNA誘導と恐怖条件付けとエストロゲンが示されました.
結論:
- PACAP-PAC1経路の障害は,PTSDの基礎となる異常なストレス反応に関与しています.
- ADCYAP1R1のエストロゲン調節によって媒介される可能性のある性特異的な効果は,PTSDの病理生理学において極めて重要です.
- PACAPレベルとADCYAP1R1 SNPは,PTSDメカニズムを理解するための貴重なバイオマーカーとして役立つ可能性があります.
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