Work

SIRT1 modulates microglia phenotypes via inhibiting drp1 phosphorylation reduces neuroinflammation in heatstroke

Year: 2024

Type: article

Abstract: BACKGROUND: Brain injury often results in high mortality rates and significant sequelae following severe heatstroke (HS). Neuroinflammation aggravates HS-induced brain injury, yet the involvement of microglia in heat-induced neuroinflammation deserves further investigation. METHODS: Our study investigated activation status, phenotype markers, production of pro-inflammatory cytokine and reactive oxygen species (ROS) of microglia both in vitro and in vivo under HS. Utilizing high-throughput sequencing, we identified SIRT1 as a potential modulator of microglia phenotype, and observed that SIRT1 alleviated severe heatstroke-induced brain injury following intraperitoneal administration of the SIRT1 agonist SRT-1720 and the inhibitor selisistat. Additionally, the effects of SRT-1720 and selisistat on mitochondrial dynamics and microglial phenotype transition were examined in BV2 cells in vitro. RESULTS: . Furthermore, the heat-induced activation of microglia was reversed by the Drp1 inhibitor, Mdivi. CONCLUSIONS: Our findings provided evidence that SIRT1 played a crucial role in inhibiting heat stress-induced microglial activation. By suppressing the phosphorylation of mitochondrial fission protein Drp1, SIRT1 contributed to the reduction of neuroinflammation and severity of heatstroke-induced brain injury.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2024.111101