Chronic Arsenic Exposure Causes Alzheimer's Disease Characteristic Effects and the Intervention of Fecal Microbiota Transplantation in Rats.

Abstract

Arsenic exposure and intestinal microbiota disorders may be related with Alzheimer's disease (AD), but the mechanism has not been elucidated. This study conducted chronic arsenic exposure from rat's maternal body to adult offspring to investigate the mechanisms of the characteristic effects of chronic arsenic exposure on AD, and further explored the intervention effect of fecal microbiota transplantation (FMT) on arsenic-mediated neurotoxicity. Transmission electron microscopy, HE staining, and related indicators were measured in the control group, the exposed group, and the FMT intervention group. Western blot was used to determine microtubule-associated proteins Tau and p-Tau₃₉₆, intestinal-brain barrier-related proteins Claudin-1 and Occludin, ELISA was used to detect the content of Aβ_1-42, and 16S rRNA sequencing was used to detect the intestinal flora of feces. Results showed that chronic arsenic exposure could lead to neurobehavioral defects in rats, increase the expression levels of Tau, p-Tau₃₉₆, and Aβ_1-42 in hippocampus (p < 0.05), increase the abundance of Clostridium _ UCG-014, decrease the abundance of Roseburia, and decrease the expression levels of Claudin-1 and Occludin in colon and hippocampus (p < 0.05). After FMT intervention, the expression levels of Tau and p-Tau₃₉₆ were decreased (p < 0.05), and the abundance of Roseburia was increased. In summary, chronic arsenic exposure caused intestinal flora disorder by changing the abundance of inflammation-related flora, thereby destroying the gut-brain barrier and causing AD characteristic effects in rats. Although the bacterial specific genus was improved and the expression of AD-related proteins was reduced after transplantation, it could not alleviate the neurobehavioral defects and neurotoxicity caused by arsenic exposure.