微生物群体可调控神经元功能
作者：
小柯机器人 发布时间：2019/10/24 15:36:30
美国康奈尔大学David Artis和Conor Liston等研究人员发现，微生物群体调节神经元功能和恐惧消退学习。相关论文发表在2019年10月24日出版的《自然》杂志上。
研究人员发现，对抗生素处理后或无菌的成年小鼠中的微生物群进行操控会导致恐惧消退学习方面的重大缺陷。大脑内侧前额叶皮层的单核RNA测序揭示了兴奋性神经元、神经胶质细胞和其他细胞类型中基因表达的显著变化。经颅双光子成像显示，成年小鼠操控微生物群后消退学习的缺陷与突触后树突棘学习相关的重塑缺陷，和内侧前额叶皮层神经元活性降低有关。
此外，微生物群体的选择性重建揭示了一个有限的幼鼠发育窗口，其中微生物群体产生的信号可以恢复成年后的正常消退学习。最后，无偏倚代谢组学分析确定了四种代谢物，这些代谢物在无菌小鼠中显著下调，并且据报道与人类和小鼠模型中的神经精神疾病有关，这表明源自微生物群的化合物可能直接影响大脑功能和行为。
总之，这些数据表明，恐惧消退学习在出生后的早期神经发育过程中和成年小鼠中都需要微生物群体来源的信号，这使得我们对饮食、感染和生活方式如何影响大脑健康以及随后对神经精神疾病的易感性的理解具有影响。
据介绍，多细胞生物与病毒、细菌、真菌和寄生虫的复杂集合体（统称为微生物群体）共同进化。在哺乳动物中，微生物群体组成的变化会影响许多生理过程（包括发育、代谢和免疫细胞功能），并与多种疾病的易感性相关。微生物群体的改变也可以调节宿主行为，例如社交活动、压力和与焦虑有关的反应，这些行为与多种神经精神疾病有关。然而，微生物群影响神经元活动和宿主行为的机制仍然不清楚。
附：英文原文
Title:The microbiota regulate neuronal function and fear extinction learning
Author:Coco Chu, Mitchell H. Murdock, Deqiang Jing, Tae Hyung Won, Hattie Chung, Adam M. Kressel, Tea Tsaava, Meghan E. Addorisio, Gregory G. Putzel, Lei Zhou, Nicholas J. Bessman, Ruirong Yang, Saya Moriyama, Christopher N. Parkhurst, Anfei Li, Heidi C. Meyer, Fei Teng, Sangeeta S. Chavan, Kevin J. Tracey, Aviv Regev, Frank C. Schroeder, Francis S. Lee, Conor Liston & David Artis
Issue&Volume:Volume 574 Issue 7779
Abstract: Multicellular organisms have co-evolved with complex consortia of viruses, bacteria, fungi and parasites, collectively referred to as the microbiota1. In mammals, changes in the composition of the microbiota can influence many physiologic processes (including development, metabolism and immune cell function) and are associated with susceptibility to multiple diseases2. Alterations in the microbiota can also modulate host behaviours—such as social activity, stress, and anxiety-related responses—that are linked to diverse neuropsychiatric disorders3. However, the mechanisms by which the microbiota influence neuronal activity and host behaviour remain poorly defined. Here we show that manipulation of the microbiota in antibiotic-treated or germ-free adult mice results in significant deficits in fear extinction learning. Single-nucleus RNA sequencing of the medial prefrontal cortex of the brain revealed significant alterations in gene expression in excitatory neurons, glia and other cell types. Transcranial two-photon imaging showed that deficits in extinction learning after manipulation of the microbiota in adult mice were associated with defective learning-related remodelling of postsynaptic dendritic spines and reduced activity in cue-encoding neurons in the medial prefrontal cortex. In addition, selective re-establishment of the microbiota revealed a limited neonatal developmental window in which microbiota-derived signals can restore normal extinction learning in adulthood. Finally, unbiased metabolomic analysis identified four metabolites that were significantly downregulated in germ-free mice and have been reported to be related to neuropsychiatric disorders in humans and mouse models, suggesting that microbiota-derived compounds may directly affect brain function and behaviour. Together, these data indicate that fear extinction learning requires microbiota-derived signals both during early postnatal neurodevelopment and in adult mice, with implications for our understanding of how diet, infection, and lifestyle influence brain health and subsequent susceptibility to neuropsychiatric disorders.
DOI:10.1038/s41586-019-1644-y
