Fusobacterium nucleatum通过表观遗传现象决定了胺诱导的行为反应的表达
Samuel J Mabry1, Xixi Cao2, Yanqi Zhu1
1University of Alabama Birmingham, Department of Surgery, Birmingham, Alabama.
bioRxiv : the preprint server for biology
|January 27, 2025
概括
细菌Fusobacterium nucleatum及其副产品丁酸盐通过增加多巴胺转运体表达来增强安非他命 (AMPH) 作用,这表明用于治疗AMPH使用障碍 (AUD) 的微生物点.
科学领域:
- 微生物学与神经科学 微生物学与神经科学
- 肠-大脑轴研究研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 胺类药物 (AMPHs) 是具有治疗用途和高滥用潜力的精神兴奋剂,导致胺使用障碍 (AUD).
- 肠道功能障碍症与AUD的发病有关,但具体的微生物机制尚不清楚.
- 在老鼠和人类中,Fusobacterium nucleatum (Fn) 的丰富性随着AMPH暴露而增加.
研究的目的:
- 调查Fn及其副产品短链脂肪酸 (SCFA) 丁酸盐在AMPH的行为影响中的机械作用.
- 为了探索基因组脱乙酶1 (HDAC1) 在Fn介导的AMPH强化中的参与.
- 阐明Fn和丁酸盐对多巴胺转运器 (DAT) 功能和胺诱导行为的影响.
主要方法:
- 基因生物Drosophila melanogaster模型被Fn殖民或补充了丁酸盐.
- 使用RNA干扰 (RNAi) 抑制了HDAC1.
- 行为测试测量了AMPH诱导的精神运动活动,奖励和性动机.
- 分析了多巴胺 (DA) 载体的功能和表达.
主要成果:
- Fn殖民或酸盐补充剂增强了AMPH在Drosophila中的精神运动,奖励和男性性激励效应.
- 仅仅抑制HDAC1就能模仿这些增强AMPH的效果.
- 酸,酸盐和HDAC1抑制增加了AMPH诱导的非膀性DA释放 (NVDR) 通过上调DAT表达.
结论:
- Fusobacterium nucleatum通过释放丁酸盐,抑制HDAC1并调节DAT表达,从而导致安非他命使用障碍.
- 这种机制通过增加多巴胺载体功能来增强AMPH的精神运动和奖励效应.
- 这些发现将Fn确定为微生物点,并建议在AUD治疗中使用益生菌干预措施.
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