Rifampicin Suppresses Amyloid-Beta Accumulation Through Enhancing Autophagy In The Hippocampus Of A Lipopolysaccharide-Induced Mouse Model Of Cognitive Decline

Background: Alzheimer's disease (AD) is characterized by amyloid-beta (A beta) deposition. The metabolism of A beta is critically affected by autophagy. Although rifampicin is known to mediate neuroinflammation, the underlying mechanism by which rifampicin regulates the cognitive sequelae remains unknown.Objective: Based on our previous findings that rifampicin possesses neuroprotective effects on improving cognitive function after neuroinflammation, we aimed to examine in this study whether rifampicin can inhibit A beta accumulation by enhancing autophagy in a mouse model of lipopolysaccharide (LPS)-induced cognitive impairment.Methods: Adult C57BL/6 mice were intraperitoneally injected with rifampicin, chloroquine, and/or LPS every day for 7 days. Pathological and biochemical assays and behavioral tests were performed to determine the therapeutic effect and mechanism of rifampicin on the hippocampus of LPS-induced mice.Results: We found that rifampicin ameliorated cognitive impairments in the LPS-induced mice. In addition, rifampicin attenuated the inhibition of autophago some formation, suppressed the accumulation of A beta(1-42), and protected the hippocamp al neurons against LPS-induced damage. Our results further demonstrated that rifampicin improved the neurological function by promoting autophagy through the inhibition of Akt/mTOR/p70S6K signaling pathway in the hippocampus of LPS-induced mice.Conclusion: Rifampicin ameliorates cognitive impairment by suppression of A beta(1-)(42) accumulation through inhibition of Akt/mTOR/p70S6K signaling and enhancement of autophagy in the hippocampus of LPS-induced mice.