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- 조회130
EMBO Mol. Med., 28 January 2025 | https://doi.org/10.1038/s44321-024-00179-y
Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors
Weonjin Yu 1,6, Yixin Xiao 1,6, Anusha Jayaraman 2,6, Yi-Chun Yen 1, Hae Ung Lee 2, Sven Pettersson 2,3,4,5,* & H Shawn Je 1,*
1Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
2ASEAN Microbiome Nutrition Centre, NationalNeuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
3Karolinska Institutet, Department of Dental Medicine, Stockholm, Sweden.
4School of Medical andLife Sciences, Sunway University, Sunway City 47500, Malaysia.
5Department of Microbiology and Immunology, National University, Singapore, Singapore.
6These authors contributed equally: Weonjin Yu, Yixin Xiao, Anusha Jayaraman.
2ASEAN Microbiome Nutrition Centre, NationalNeuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
3Karolinska Institutet, Department of Dental Medicine, Stockholm, Sweden.
4School of Medical andLife Sciences, Sunway University, Sunway City 47500, Malaysia.
5Department of Microbiology and Immunology, National University, Singapore, Singapore.
6These authors contributed equally: Weonjin Yu, Yixin Xiao, Anusha Jayaraman.
*Corresponding authors: correspondence to Sven Pettersson or H Shawn Je
Abstract
Changes in gut microbiota composition have been linked to anxiety behavior in rodents. However, the underlying neural circuitry linking microbiota and their metabolites to anxiety behavior remains unknown. Using male C57BL/6J germ-free (GF) mice, not exposed to live microbes, increased anxiety-related behavior was observed correlating with a significant increase in the immediate early c-Fos gene in the basolateral amygdala (BLA). This phenomenon coincided with increased intrinsic excitability and spontaneous synaptic activity of BLA pyramidal neurons associated with reduced small conductance calcium-activated potassium (SK) channel currents. Importantly, colonizing GF mice to live microbes or the microbial-derived metabolite indoles reverted SK channel activities in BLA pyramidal neurons and reduced the anxiety behavioral phenotype. These results are consistent with a molecular mechanism by which microbes and or microbial-derived indoles, regulate functional changes in the BLA neurons. Moreover, this microbe metabolite regulation of anxiety links these results to ancient evolutionarily conserved defense mechanisms associated with anxiety-related behaviors in mammals.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-02-06)
- 국외 연구진
- 생명과학 > 생리학
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