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Biomed Pharmacother ; 129: 110449, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32768944

ABSTRACT

Manganese (Mn) exposure has been reported to cause neurodegenerative disorders. ß-Amyloid (Aß) induced Tau pathology in an NLRP3-dependent manner is at the heart of Alzheimer's and Parkinson's diseases. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. In this study, we found that Mn exposure increases Aß1-40 and Tau production in brain, and causes hippocampal degeneration and necrosis. Meanwhile, Mn exposure can stimulate neurotoxicity by increasing inflammation either in peripheral blood and CNS. Importantly, we found that transplantation of gut microbiota from normal rats into Mn exposure rats reduced Aß and Tau expression, and the cerebral expression of NLRP3 was downregulated, and the expression of neuroinflammatory factors was also downregulated. Therefore, improving the composition of gut microbiota in Mn exposure rats can attenuate neuroinflammation, which is considered as a novel therapeutic strategy for Mn exposure by remodelling the gut microbiota.


Subject(s)
Cerebral Cortex/metabolism , Gastrointestinal Microbiome , Inflammasomes/metabolism , Intestines/microbiology , Manganese Poisoning/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Amyloid beta-Peptides/metabolism , Animals , Cerebral Cortex/pathology , Cytokines/metabolism , Disease Models, Animal , Fecal Microbiota Transplantation , Male , Manganese Poisoning/microbiology , Manganese Poisoning/pathology , Manganese Poisoning/prevention & control , Peptide Fragments/metabolism , Rats, Sprague-Dawley , tau Proteins/metabolism
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