Research Paper Volume 13, Issue 11 pp 15240—15254
Depletion of SENP1-mediated PPARγ SUMOylation exaggerates intermittent hypoxia-induced cognitive decline by aggravating microglia-mediated neuroinflammation
- 1 The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China
- 2 Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
- 3 China Medical University, Shenyang 110122, Liaoning, China
- 4 Affiliated Zhengzhou People's Hospital, The Second School of Clinical Medicine, Southern Medical University, Zhengzhou 450003, Henan, China
Received: December 27, 2020 Accepted: May 13, 2021 Published: May 25, 2021https://doi.org/10.18632/aging.203084
How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Intermittent hypoxia (IH)-associated cognition decline is related to the neuroinflammation of microglia. SUMOylation is a post-translational modification related to multiple human diseases, which can be reversed by SENP1. Studies showed that SENP1 and PPARγ play essential roles in restricting inflammation by blocking NF-κB activation. However, the mechanism remains unclear. Herein, we investigated the precise mechanism underlying SENP1 and PPARγ in cognitive decline after IH insult. Biochemical analysis results revealed that IH triggered the inflammatory response and neuronal apoptosis, increased the SUMOylation of PPARγ, and decreased the level of PPARγ compared to that in the normoxia group. After SENP1 downregulation, the inflammatory response, neuronal apoptosis and the SUMOylation of PPARγ were enhanced, and the level of PPARγ was further decreased in vitro and in vivo. However, the application of PPARγ agonist, GW1929, abolished the enhancement of inflammation and neuronal apoptosis in vitro. The Morris Water Maze results showed that both IH groups mice exhibited longer latency and shorter dwell-time in the goal quadrant than normoxia groups. Notably, SENP1 downregulation aggravated these alterations. Overall, these results showed that SENP1 played an essential role in IH-associated cognitive dysfunction. SENP1 depletion aggravated neuroinflammation and neuronal apoptosis via promoting the SUMOylation of PPARγ, reducing the level of PPARγ, thus exaggerating IH-induced cognitive decline.