Maf1 mitigates sevoflurane-induced microglial inflammatory damage and attenuates microglia-mediated neurotoxicity in HT-22 cells by activating the AMPK/Nrf2 signaling

  • Neurotoxicology. 2022 May;90:237-245. doi: 10.1016/j.neuro.2022.04.003.
Yunyi Dai  1 ,  Mingguang Yan  2 ,  Juan Wan  3 ,  Tao Xiao  4
Affiliations
  • 1. Department of Neurology, The First People's Hospital of Shangqiu, China.
  • 2. Department of Laboratory Medicine, The First People's Hospital of Shangqiu, China.
  • 3. Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, China.
  • 4. Department of Neurosurgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, China. Electronic address: [email protected].
PMID: 35430185 DOI: 10.1016/j.neuro.2022.04.003
Abstract

Background: Maf1 has been found to play protective function against neuroinflammation and neuroapoptosis. This study seeks to explore whether and how Maf1 is involved in sevoflurane (Sev)-induced neuroinflammation and microglia-mediated neurotoxicity.

Methods: qRT-PCR and western blot were used to detect the gene expression. ELISA was used to detect inflammatory factors. Cell viability was evaluated by using the Cell Counting Kit-8 kit. Neuroapoptosis was assessed with trhe Caspase-3 Assay Kit and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique.

Results: Maf1 expression was downregulated in Sev-stimulated BV2 microglial cells. Maf1 overexpression down-regulates the expression of pro-inflammatory M1-type markers (CD86, iNOS, IFN-γ) and up-regulates the expression of anti-inflammatory M2-type markers (CD206, TGF-β, Arg-1), and Maf1 reduces the Sev-induced inflammatory response in BV2 cells. After Maf1 overexpression, the relative expression of p-AMPK/AMPK and nucleus-Nrf2 increased significantly in BV2 cells treated with Sev. Inhibition of AMPK/Nrf2 pathway by compound C reverses anti-inflammatory effect of Maf1 in Sev-stimulated BV2 cells. Compound C reverses the effect of Maf1 on microglia-mediated neurotoxicity in HT-22 hippocampal neuronal cells.

Conclusions: Maf1 mitigates Sev-induced microglial inflammatory damage and attenuates microglia-mediated neurotoxicity by activating the AMPK/Nrf2 signaling.

Keywords
Maf1; Microglia; Neuroinflammation; Sev.
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