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生命早期肠道微生物群缺失会影响小鼠海马的抗焦虑行为和单胺神经递质系统。

Absence of gut microbiota during early life affects anxiolytic Behaviors and monoamine neurotransmitters system in the hippocampal of mice.

机构信息

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

J Neurol Sci. 2019 May 15;400:160-168. doi: 10.1016/j.jns.2019.03.027. Epub 2019 Mar 29.

DOI:
10.1016/j.jns.2019.03.027
PMID:30954660
Abstract

The gut microbiome is composed of an enormous number of microorganisms, generally regarded as commensal bacteria. Resident gut bacteria are an important contributor to health and significant evidence suggests that the presence of healthy and diverse gut microbiota is important for normal cognitive and emotional processing. Here we measured the expression of monoamine neurotransmitter-related genes in the hippocampus of germ-free (GF) mice and specific-pathogen-free (SPF) mice to explore the effect of gut microbiota on hippocampal monoamine functioning. In total, 19 differential expressed genes (Htr7, Htr1f, Htr3b, Drd3, Ddc, Maob, Tdo2, Fos, Creb1, Akt1, Gsk3a, Pik3ca, Pla2g5, Cyp2d22, Grk6, Ephb1, Slc18a1, Nr4a1, Gdnf) that could discriminate between the two groups were identified. Interestingly, GF mice displayed anxiolytic-like behavior compared to SPF mice, which were not reversed by colonization with gut microbiota from SPF mice. Besides, colonization of adolescent GF mice by gut microbiota was not sufficient to reverse the altered gene expression associated with their GF status. Taking these findings together, the absence of commensal microbiota during early life markedly affects hippocampal monoamine gene-regulation, which was associated with anxiolytic behaviors and monoamine neurological signs.

摘要

肠道微生物组由大量微生物组成,通常被认为是共生细菌。肠道常驻细菌是健康的重要贡献者,有大量证据表明,健康多样的肠道微生物群对于正常的认知和情绪处理很重要。在这里,我们测量了无菌(GF)小鼠和特定病原体自由(SPF)小鼠海马中单胺神经递质相关基因的表达,以探讨肠道微生物群对海马中单胺能功能的影响。共有 19 个差异表达基因(Htr7、Htr1f、Htr3b、Drd3、Ddc、Maob、Tdo2、Fos、Creb1、Akt1、Gsk3a、Pik3ca、Pla2g5、Cyp2d22、Grk6、Ephb1、Slc18a1、Nr4a1、Gdnf)可以区分这两组。有趣的是,与 SPF 小鼠相比,GF 小鼠表现出类似焦虑的行为,而这种行为不能通过 SPF 小鼠的肠道微生物群定植来逆转。此外,青春期 GF 小鼠的肠道微生物群定植不足以逆转与 GF 状态相关的基因表达改变。综上所述,生命早期共生微生物群的缺失显著影响海马中单胺能基因调控,与焦虑样行为和单胺能神经症状有关。

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