相关实验视频
创伤后应激障碍与PACAP和PAC1受体有关
Kerry J Ressler1, Kristina B Mercer, Bekh Bradley
1Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. kressle@emory.edu
Nature
|February 26, 2011
概括
在创伤后应激障碍 (PTSD) 中,垂体腺酸环酶激活多 (PACAP) 途径的参与是性别特异的. 较低的PACAP水平和特定的基因变异与女性的PTSD症状有关,这表明一种潜在的生物标志物.
科学领域:
- 神经生物学 神经生物学 神经生物学
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
背景情况:
- pituitary adenylate cyclase-activating polypeptide (PACAP) 在很大程度上调节了细胞的应激反应.
- 在人类心理压力,特别是创伤后应激障碍 (PTSD) 中,PACAP-PAC1受体通路的作用仍然不清楚.
研究的目的:
- 研究PACAP-PAC1通路与PTSD之间的关联,重点关注性别特异性影响.
- 在PACAP途径中识别潜在的PTSD遗传和分子生物标志物.
主要方法:
- 在ADCYAP1和ADCYAP1R1基因中检查了44个单核酸多态 (SNP) 与PTSD诊断和症状相关.
- 在人类受试者中评估了PACAP血液水平,恐惧生理学和ADCYAP1R1 mRNA表达.
- 利用动物模型研究在恐惧调节和雌激素替代下ADCYAP1R1mRNA诱导.
主要成果:
- 在女性中,PACAP血液水平和PTSD之间发现了性别特定的关联.
- 在ADCYAP1R1中,一个特定的SNP (rs2267735) 与PTSD诊断和症状显著相关,仅在女性中.
- 这种SNP与人类大脑中的恐惧歧视和ADCYAP1R1 mRNA表达相关,ADCYAP1R1甲基化与PTSD有关.
- 动物研究显示ADCYAP1R1mRNA诱导与恐惧调节和雌激素.
结论:
- 在PACAP-PAC1通路中的乱与背后的PTSD背后的异常压力反应有关.
- 性别特异性影响,可能由ADCYAP1R1的雌激素调节介导,在PTSD病理生理学中至关重要.
- PACAP水平和ADCYAP1R1SNP可以作为了解PTSD机制的宝贵生物标志物.
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