减弱的葡萄皮质激素对压力的反应会导致行为和生物学变化,导致创伤后应激障碍的脆弱性
Silvia Monari1, Isabelle Guillot de Suduiraut2, Jocelyn Grosse2
1Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Biological psychiatry
|September 24, 2023
概括
减弱的皮质糖类水平,而不是海马的大小,在大鼠模型中因果驱动恐惧灭绝缺陷和快速眼动睡眠障碍,为创伤后应激障碍的脆弱性提供了新的见解.
科学领域:
- 神经科学是一个神经科学.
- 行为生物学 行为生物学
- 压力研究 压力研究
背景情况:
- 创伤后应激障碍 (PTSD) 仅影响受创伤影响的个体的一个子集,需要识别脆弱性因素.
- 潜在的危险因素包括行为 (恐惧灭绝缺陷) 和生物学 (低葡萄皮质类药物,小海马体,REM睡眠障碍) 特性.
- 这些特征之间的相互关系和因果关系在很大程度上是未知的.
研究的目的:
- 在与PTSD相关的老鼠模型中研究特定生物行为特征的相互关系和因果作用.
- 为了确定是否减弱的葡萄糖皮质激素反应因果影响恐惧灭绝,海马体积和快速眼动睡眠 (REMS) 障碍.
主要方法:
- 利用一种经过基因选择的老鼠模型,对皮质激素压力反应进行了削弱.
- 采用了ex-vivoMRI,带有恐惧的调节,以及使用体内摄影仪的多睡眠学.
- 评估了生物行为特征和后期皮质激素管理的影响.
主要成果:
- 对于减弱的葡萄糖皮质激素反应的遗传选择与受损的恐惧灭绝 (男性),较小的海马体积和REMS障碍相关.
- 灭绝后的皮质正常化了恐惧灭绝缺陷和REMS干扰,表明对葡萄糖皮质缺乏的因果作用.
- 减少REMS与海马内上升的上腺素有关,这种情况也因皮质激素治疗而逆转.
结论:
- 葡萄糖皮质激素缺乏在REMS变化和恐惧灭绝缺陷中起着主导作用,比降低海马体积更重要.
- 削弱的葡萄皮质类药物有助于引起神经生理学障碍,这些障碍是恐惧灭绝障碍的基础.
- 研究结果表明,葡萄糖皮质体功能是PTSD易受伤害和神经生物学失调的关键因素.
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