Sirtuin 1 alleviates microglia-induced inflammation by modulating the PGC-1α/Nrf2 pathway after traumatic brain injury in male rats.

Abstract

Microglial activation and the subsequent inflammatory response play important roles in the central nervous system after traumatic brain injury (TBI). Activation of the PGC-1α pathway is responsible for microglial activation after TBI. Our previous study demonstrated that SIRT1 alleviates neuroinflammation-induced apoptosis after TBI, and activation of the PGC-1α/Nrf2 pathway extenuates TBI-induced neuronal apoptosis. However, no study has investigated whether SIRT1 can affect the PGC-1α/Nrf2 pathway to induce microglial excitation and the subsequent neuroinflammatory response. Microglial activation and the levels of pro-inflammatory factors, namely, tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were assessed to evaluate the neuroinflammatory response after TBI. To examine the effects of SIRT1, immunohistochemical staining and western blot analysis were used to observe the nuclear translocation and secretion of PGC-1α, as well as the activation of the PGC-1α/Nrf2 pathway. Treatment with the SIRT1 inhibitor sirtinol promoted microglial activation and pro-inflammatory factor expression (TNF-α, IL-6, and IL-1β) and inhibited PGC-1α and Nrf2 nuclear translocation and secretion after TBI, while treatment with the SIRT1 activator A3 had the opposite effects. The results of this study suggest that microglial activation, the subsequent neuroinflammatory response, and the PGC-1α/Nrf2 pathway play essential roles in secondary injury after TBI. These results indicate that SIRT1 protects neurons after TBI by inhibiting microglial activation and the subsequent inflammatory response, possibly by activating the PGC-1α/Nrf2 pathway.

• Authors: Xiangrong Chen, Guan Wei, Ding Li, Youwu Fan, Yile Zeng, Zhengting Qian, Zhen Jia, Yong Tang, Yan Shi, Heming Wu, Xiang Li
• Journal: Brain research bulletin (Brain Res Bull) Vol. 185 Pg. 28-38 (07 2022) ISSN: 1873-2747 [Electronic] United States
• PMID: 35487384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-6
• NF-E2-Related Factor 2
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Tumor Necrosis Factor-alpha
• Sirtuin 1

Topics

• Animals
• Brain Injuries, Traumatic (pathology)
• Inflammation (metabolism)
• Interleukin-6 (metabolism)
• Male
• Microglia (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism, pharmacology)
• Rats
• Signal Transduction
• Sirtuin 1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)