title: Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate.
abstract: Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.
authors.affiliation: Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China ; School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xichong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Zongxin
authors.initials: Z
authors.lastname: Ling
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Haixiao
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Mengqi
authors.initials: M
authors.lastname: Pang
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yu
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Jiru
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000382:microbiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology; D046972:Clostridium butyricum; D015140:Dementia, Vascular / Q000628:therapy*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D019936:Probiotics / Q000627:therapeutic use*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002087:Butyrates; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases