Fusobacterium nucleatum通过一个由丁酸盐驱动的表观遗传机制增强了安非他胺诱导的行为反应
Samuel J Mabry1, Xixi Cao2, Yanqi Zhu1
1Department of Surgery, University of Alabama Birmingham, Birmingham, AL 35233, USA.
Science signaling
|September 9, 2025
概括
肠道细菌,如Fusobacterium nucleatum及其副产品丁酸盐,可以放大安非他胺的作用. 这通过影响多巴胺信号的表观遗传变化发生,这表明治疗安非他命使用障碍 (AUD) 的新目标.
科学领域:
- 神经科学是一个神经科学.
- 微生物学 微生物学
- 遗传学 遗传学 是一个
背景情况:
- 胺类是具有治疗用途的精神兴奋剂,但容易滥用,导致胺使用障碍 (AUD).
- AUD的致病性涉及肠道微生物组的失调和细菌代谢物,如短链脂肪酸 (SCFA),影响肠-大脑轴.
- 暴露于安非他胺会增加肠道Fusobacterium nucleatum,一种产生SCFA的细菌.
研究的目的:
- 调查Fusobacterium nucleatum及其代谢物丁酸盐在调节安非他胺效应中的作用.
- 探索潜在的表观遗传机制,特别是素脱乙酶 (HDAC) 抑制,在安非他胺诱导的行为.
- 阐明F.核和丁酸盐如何影响多巴胺信号传递和非膀性多巴胺释放 (NVDR).
主要方法:
- 使用 gnotobiotic Drosophila melanogaster 模型与 F. nucleatum 定居或食酸盐.
- 进行了HDAC1的淘汰,以评估其在介导F. nucleatum和丁酸盐效应中的作用.
- 测量了安非他胺诱导的精神运动活动,奖励特性,多巴胺水平以及多巴胺载体 (DAT) 功能和表达.
主要成果:
- 在Drosophila中,F. nucleatum殖民或丁酸盐补充增强了安非他胺的精神运动和奖励效应.
- 降低HDAC1模仿了F.核和丁酸盐的影响,表明HDAC抑制参与其中.
- 这些增强与通过反向DAT功能 (NVDR) 增加多巴胺释放有关,部分原因是由F. nucleatum或butyrate刺激的DAT表达升调.
结论:
- 菌核酸和其代谢物丁酸盐可以通过表观遗传调节多巴胺信号传递来增强安非他命的作用.
- 这些发现突出了一个机制,肠道细菌通过改变多巴胺转运体表达和功能来影响AUD.
- F.核和丁酸盐代表了管理胺使用障碍的潜在治疗点.
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