title: Microbiota Modulates Behavior and Protein Kinase C mediated cAMP response element-binding protein Signaling.
abstract: Evolutionary pressure drives gut microbiota-host coevolution and results in complex interactions between gut microbiota and neural development; however, the molecular mechanisms by which the microbiota governs host behavior remain obscure. Here, we report that colonization early in life is crucial for the microbiota to modulate brain development and behavior; later colonization or deletion of microbiota cannot completely reverse the behaviors. Microarray analysis revealed an association between absence of gut microbiota and expression in cAMP responding element-binding protein (CREB) regulated genes in the hippocampus. The absence of gut microbiota from birth was shown to be associated with decreased CREB expression, followed by decreases of protein kinase C beta (PRKCB) and AMPA receptors expression, and an increase of phosphorylation CREB (pCREB) expression. Microbiota colonization in adolescence restored CREB and pCREB expression, but did not alter PRKCB and AMPARs expression. The removal of the gut microbiota from SPF mice using antibiotics only reduced pCREB expression. These findings suggest that (i) colonization of the gut microbiota early in life might facilitate neurodevelopment via PKC-CREB signaling and (ii) although GF mice and ABX mice display reduced anxiety-related behaviors, the molecular mechanisms behind this might differ.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Benhua
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Huo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Chongqing Cancer Hospital &Institute &Cancer Center, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.|Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.|Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.|South Australian Health and Medical Research Institute, Mind and Brain Theme, and Flinders University, Adelaide, SA, Australia.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D064546:Protein Kinase C beta / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D064546:Protein Kinase C beta