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在催化素受体+细胞中异常的TSC-Rheb轴调解压力诱导的焦虑
Olivia Tabaka1, Saheed Lawal1, Rodrigo Del Rio Triana2
1Department of Neurobiology & Behavior, Stony Brook University, Stony Brook, NY 11794.
bioRxiv : the preprint server for biology
|July 9, 2024
概括
研究人员通过改变氧化受体细胞中的Tsc2来模拟结核硬化综合体 (TSC) 中的焦虑. 性差异出现在应激反应中,男性避免引起焦虑的情况,女性表现出性. 抑制综合应激反应 (ISR) 在两性中使行为正常化.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 行为科学 行为科学
背景情况:
- 病理性焦虑是适应不良过程的重要风险因素,影响多达59%的结核性硬化综合体 (TSC) 患者.
- TSC是一种神经发育障碍,源于TSC1/TSC2基因的突变,影响结核素和哈马丁蛋白质复合体的功能.
- 边缘前脑中异常的催产素信号与压力诱导的行为回避和焦虑有关.
研究的目的:
- 在结核性硬化综合体 (TSC) 中模拟病理焦虑类行为,通过在催产素受体细胞 (OTRC) 中产生细胞类型特定的 Tsc2 淘汰.
- 在TSC小鼠模型中研究社会隔离压力对焦虑类行为和社会互动的性别特异效应.
- 探索综合应激反应 (ISR) 和中间前额叶皮层 (mPFC) 催产素受体细胞 (OTRCs) 在调节TSC的情绪反应中的作用.
主要方法:
- 在催产素受体细胞 (OTRCs) 中产生细胞类型特定的Tsc2异构体淘汰,以建模TSC.
- 暴露在条件异构体小鼠长时间的社会隔离,以诱导压力和评估方法避免冲突行为.
- 利用整合应激反应 (ISR) 的全身和中间前额叶皮层 (mPFC) 特定抑制来评估其对行为的影响.
主要成果:
- 社会上孤立的男性突变体在焦虑环境中表现出行为回避,并寻求社交互动以缓冲压力.
- 女性突变者表现出对社会隔离的弹性,接近焦虑性环境并低社会互动的价值.
- 抑制ISR使男性和女性突变者的接近行为正常化;OTRC中的Tsc2缺失导致男性的低面性,由ISR抑制缓解.
结论:
- 前额前氧化受体细胞 (OTRCs) 在调节结核性硬化综合体 (TSC) 中对焦虑性环境的情绪反应中起着两形性作用.
- 在TSC模型中,综合应激反应 (ISR) 是这些性二态行为的关键调解者.
- 结果表明,在TSC和其他NDD中,以细胞自主ISR和前额前线网络抑制为特征的焦虑亚型的潜在治疗点.
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