https://scholars.lib.ntu.edu.tw/handle/123456789/634569
Title: | Microbial metabolites regulate social novelty via CaMKII neurons in the BNST | Authors: | Liou, Chia-Wei Cheng, Sin-Jhong Yao, Tzu-Hsuan Lai, Tzu-Ting Tsai, Yu-Hsuan Chien, Che-Wei Kuo, Yu-Lun Chou, Shih-Hsuan CHENG-CHIH HSU Wu, Wei-Li |
Keywords: | Bed nucleus of stria terminalis (BNST); Calcium/calmodulin-dependent protein kinase II (CaMKII); Cerebrospinal fluid (CSF); Fatty acid oxidation; Gut-brain axis; Gut-derived metabolites; Lateral ventricle; Microbiota; Short-chain fatty acids (SCFAs); Social novelty | Issue Date: | 29-Jun-2023 | Journal Volume: | 113 | Start page/Pages: | 104 | Source: | Brain, behavior, and immunity | Abstract: | Social novelty is a cognitive process that is essential for animals to interact strategically with conspecifics based on their prior experiences. The commensal microbiome in the gut modulates social behavior through various routes, including microbe-derived metabolite signaling. Short-chain fatty acids (SCFAs), metabolites derived from bacterial fermentation in the gastrointestinal tract, have been previously shown to impact host behavior. Herein, we demonstrate that the delivery of SCFAs directly into the brain disrupts social novelty through distinct neuronal populations. We are the first to observe that infusion of SCFAs into the lateral ventricle disrupted social novelty in microbiome-depleted mice without affecting brain inflammatory responses. The deficit in social novelty can be recapitulated by activating calcium/calmodulin-dependent protein kinase II (CaMKII)-labeled neurons in the bed nucleus of the stria terminalis (BNST). Conversely, chemogenetic silencing of the CaMKII-labeled neurons and pharmacological inhibition of fatty acid oxidation in the BNST reversed the SCFAs-induced deficit in social novelty. Our findings suggest that microbial metabolites impact social novelty through a distinct neuron population in the BNST. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/634569 | ISSN: | 08891591 | DOI: | 10.1016/j.bbi.2023.06.029 |
Appears in Collections: | 化學系 |
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