首页|Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway

Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway

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Increased intestinal barrier permeability,leaky gut,has been reported in patients with autism.However,its contribution to the development of autism has not been determined.We selected dextran sulfate sodium(DSS)to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis.DSS treat-ment resulted in a decreased affinity for social proximity;however,autistic behaviors in mice were improved after the administration of metformin.We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors.The concentration of lipopol-ysaccharides in blood decreased after the administration of metformin.The expression levels of the key molecules in the toll-like receptor 4(TLR4)-myeloid differentiation factor 88(MyD88)-nuclear factor kappa B(NF-κB)pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed.Thus,"leaky gut"could be a trigger for the development of autism via activation of the lipopolysac-charide-mediated TLR4-MyD88-NF-KB pathway.

AutismGutLipopolysaccharideToll-like receptor 4Metformin

Fang Li、Haoran Ke、Siqi Wang、Wei Mao、Cexiong Fu、Xi Chen、Qingqing Fu、Xiaori Qin、Yonghua Huang、Bidan Li、Shibing Li、Jingying Xing、Minhui Wang、Wenlin Deng

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Department of Gastroenterology,Gastroenterology Endoscopy Center,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

Hepatology Unit,Department of Infectious Diseases,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China

Department of Gastroenterology,First Affiliated Hospital of Guangzhou Medical University,Guangzhou Medical University,Guangzhou 510120,China

Department of Hepatopancreatobiliary Surgery,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

Otolaryngology-Head and Neck Surgery,Hospital of Hainan Province,Department of Otorhinolaryngology,Head and Neck Surgery,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

Department of Radiology,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

Department of Pediatric Surgery,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

Department of Gastroenterology,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

Department of Nephrology,Department of Nephrology,Hainan Affiliated Hospital of Hainan Medical College,Hainan General Hospital,Haikou 570311,China

Department of Pediatrics,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China

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National Natural Science Foundation of ChinaHainan Provincial Natural Science Foundation of China

82100609821QN0982

2023

10.1007/s12264-022-00993-9

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(6)
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