微质I型干扰素信号传递介导慢性压力诱导的突触损失和社会行为缺陷
Ashutosh Tripathi1, Alona Bartosh1, Jocelyn Mata1
1Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Molecular psychiatry
|August 2, 2024
概括
I型干扰素 (IFN-I) 在微质中发出信号,导致经历慢性压力后的突触损失和社会行为缺陷. 在这些细胞中阻断IFN-I受体 (IFNAR) 恢复了小鼠的正常社会功能和突触完整性.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 行为科学 行为科学
背景情况:
- 突触损失和炎症与神经精神疾病有关.
- 慢性压力通过减少前额叶皮层 (PFC) 中的树突状棘来损害社会行为.
- 压力诱导的突触损失背后的机制尚不清楚.
研究的目的:
- 调查I型干扰素 (IFN-I) 信号在慢性不可预测压力 (CUS) 引起的突触损失和行为缺陷中的作用.
- 在压力期间探索PFC中微质IFN-I受体 (IFNAR) 的功能.
主要方法:
- 利用一种慢性不可预测压力 (CUS) 的小鼠模型.
- 雇佣了微质IFNAR的条件淘汰.
- 在PFC组织上进行大量RNA测序.
- 评估了社会行为和突触完整性.
主要成果:
- 在PFC中,CUS增加了微质IFNAR表达.
- 条件淘汰微质IFNAR拯救了CUS诱导的社会行为缺陷和突触损失.
- 微质中的IFNAR缺失减弱了CUS诱导的Krt20,Cldn5和Nr4a1基因表达的变化.
- 克尔特20的减少表明,细胞激素在压力诱导的神经可塑性改变中的新角色.
结论:
- 在应对慢性压力时,微质IFNAR信号传递对于调解突触损失和社会行为缺陷至关重要.
- 向微质IFNAR可能为与压力相关的神经精神疾病提供治疗潜力.
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