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星体细胞核中的CREB促进了对慢性压力的敏感性
Leanne M Holt1, Trevonn M Gyles1, Eric M Parise1
1Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
bioRxiv : the preprint server for biology
|January 31, 2024
概括
大脑中的星球细胞.
科学领域:
- 神经科学是一个神经科学.
- 分子精神病学分子精神病学
- 天星细胞生物学 天星细胞生物学
背景情况:
- 星球细胞越来越多地与压力和严重抑郁症 (MDD) 有关.
- 星体细胞核对压力的转录反应 (NAc) 仍然在很大程度上未知.
- 了解NAc天体细胞应激反应对于阐明它们在抑郁症中的作用至关重要.
研究的目的:
- 在遭受慢性社会失败压力 (CSDS) 的雄性小鼠中研究NAc天体细胞的转录组.
- 为了确定在应对压力时天体细胞转录变化的上游调节者.
- 确定天体细胞CREB在压力诱导的类似抑郁的行为中的作用.
主要方法:
- 使用全细胞分类和RNA测序来分析NAc天体细胞转录组.
- 生物信息分析预测了上游监管机构,包括CREB.
- 免疫组织化学和在星球细胞中对CREB的病毒媒介操纵被用来验证发现并评估行为影响.
主要成果:
- 在应激敏感和应激抗性小鼠中,CSDS诱导了NAc天体细胞中显著的转录反应.
- 鉴定出CREB是天体细胞转录组的关键上游调节器,在性与易受性小鼠中具有差异性的激活状态.
- 在NAc星球细胞中CREB的过度表达促进了对慢性压力和类似抑郁症的行为敏感性.
结论:
- 天体细胞转录组对慢性社会失败压力做出强有力的反应.
- 天体细胞内的转录调节有助于发展类似抑郁症的行为.
- 准天体细胞转录通路可能为神经精神疾病提供新的治疗策略.
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