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Research Article| Volume 400, P160-168, May 15, 2019

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

  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    Jun-Xi Pan
    Footnotes
    1 These authors contributed equally to the manuscript.
    Affiliations
    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
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  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    Feng-Li Deng
    Footnotes
    1 These authors contributed equally to the manuscript.
    Affiliations
    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
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  • Ben-Hua Zeng
    Affiliations
    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 Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, 400038 Chongqing, China
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  • Peng Zheng
    Affiliations
    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
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  • Wei-Wei Liang
    Affiliations
    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
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  • Bang-Min Yin
    Affiliations
    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
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  • Jing Wu
    Affiliations
    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
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  • Mei-Xue Dong
    Affiliations
    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
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  • Yuan-Yuan Luo
    Affiliations
    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
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  • Hai-Yang Wang
    Affiliations
    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
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  • Hong Wei
    Correspondence
    Correspondence to: H. Wei, Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Gaotanyan Street, Chongqing 400038, China.
    Affiliations
    Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, 400038 Chongqing, China
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  • Peng Xie
    Correspondence
    Correspondence to: P. Xie, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, 400016 Chongqing, China.
    Affiliations
    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
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to the manuscript.
Published:March 29, 2019DOI:https://doi.org/10.1016/j.jns.2019.03.027

      Highlights

      • A comprehensive global evaluation of the hippocampal monoamine neurotransmitters in germ-free (GF) mice.
      • Absence of gut microbiota markedly affects hippocampal monoamine genes, impairing the development of brain and behaviors.
      • Altered anxiolytic behaviors and monoamine genes induced by GF status could't be reversed by colonization at adolescence.

      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.

      Keywords

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