Abstract
Sepsis-associated encephalopathy (SAE) is a common and serious complication of sepsis, which is thought to be caused by neuroinflammation. In our previous study, ubiquitin-specific protease 8 (USP8), was reported to regulate inflammation in vitro. In the current study, we investigated whether increased USP8 expression would ameliorate the cognitive and motor impairments induced by cecal ligation and puncture (CLP) in mice, a model of SAE. Male adult mice were randomly divided into four groups: control, sham, CLP, and CLP + USP8 groups. The CLP + USP8 mice showed reduced weight loss on day 4 post-CLP, with a slight increase noted on day 7. The mortality rate in the CLP group was 70% 48 h after CLP; however, USP8 significantly improved survival after CLP. USP8 modulated the neurobehavioral scores in CLP mice. Our results also indicate that USP8 attenuated the CLP-induced cognitive and motor impairments, based on the performance of mice in the Morris water maze (MWM), pole-climbing, and wire suspension tests. USP8 suppressed the release of pro-inflammatory mediators, including prostaglandin E2(PGE2) in the serum and nitric oxide (NO) in brain tissue, as well as levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in brain tissue. Immunofluorescence experiments revealed that USP8 inhibited CLP-induced increases in microglial size and density in the hippocampus, and protected hippocampal neurons. Our findings indicate that neuroinflammation occurs in the brains of CLP mice, and that USP8 exerts protective effects against CLP-induced neuroinflammation and cognitive and motor impairments, which may aid in the development of novel therapeutic strategies for SAE.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.