Abstract
Intermittent hypoxia (IH)‐induced cognition decline is related to the neuroinflammation in microglia. SUMOylation is associated with multiple human diseases, which can be reversed by sentrin/SUMO‐specific proteases 1 (SENP1). Herein, we investigated the role of SENP1 in IH‐induced inflammation and cognition decline. BV‐2 microglial cells and mice were used for inflammatory response and cognition function evaluation following IH treatment. Biochemical analysis and Morris water maze methods were used to elaborate the mechanism of SENP1 in IH impairment. Molecular results revealed that IH induced the inflammatory response, as evidenced by the up‐regulation of NF‐κB activation, IL‐1β and TNF‐α in vitro and in vivo. Moreover, IH decreased the expression of SENP1, and increased the SUMOylation of NEMO, not NF‐κB P65. Moreover, SENP1 overexpression inhibited IH‐induced inflammatory response and SUMOylation of NEMO. However, the inhibitions were abolished by siRNA‐NEMO. In contrast, SENP1 depletion enhanced IH‐induced inflammatory response and SUMOylation of NEMO, accompanying with increased latency and reduced dwell time in mice. Overall, the results demonstrated that SENP1 regulated IH‐induced neuroinflammation by modulating the SUMOylation of NEMO, thus activating the NF‐κB pathway, revealing that targeting SENP1 in microglia may represent a novel therapeutic strategy for IH‐induced cognitive decline.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
