1. Academic Validation
  2. MiR-124 Prevents the Microglial Proinflammatory Response by Inhibiting the Activities of TLR4 and Downstream NLRP3 in Palmitic Acid-Treated BV2 Cells

MiR-124 Prevents the Microglial Proinflammatory Response by Inhibiting the Activities of TLR4 and Downstream NLRP3 in Palmitic Acid-Treated BV2 Cells

  • J Mol Neurosci. 2022 Mar;72(3):496-506. doi: 10.1007/s12031-021-01921-8.
Caixia Yang 1 Guanghong Sui 2 Lu Wang 3 Zheng Chen 4 Feng Wang 5 6
Affiliations

Affiliations

  • 1 Department of Rehabilitation, Tianjin Anding Hospital, Tianjin, 300074, China.
  • 2 Department of Child and Adolescent Psychology, Tianjin Anding Hospital, Tianjin, 300074, China.
  • 3 Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
  • 4 Department of Psychology, Tianjin Anding Hospital, No. 13, Liulin Road, Hexi District, Tianjin, 300074, China. [email protected].
  • 5 Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, No. 154, Anshan Road, Heping District, Tianjin, 300052, China. [email protected].
  • 6 Department of Psychology, Tianjin Anding Hospital, No. 13, Liulin Road, Hexi District, Tianjin, 300074, China. [email protected].
Abstract

Neuroinflammation is a mechanism by which obesity or a high-fat diet leads to cognitive impairment. MiR-124, a highly expressed MicroRNA in the brain, can alleviate neuroinflammation by regulating microglial activation, but its mechanism is unclear. The aim of the study was to explore whether miR-124 exerted this effect through TLR4/MyD88/NF-κB p65/NLRP3 signaling in palmitic acid-treated BV2 cells. Prepared BV2 cells were treated with palmitic acid to establish an in vitro model of a high-fat diet. An miR-124 mimic and inhibitor were adopted to upregulate and downregulate the expression of miR-124, respectively. TAK-242 and NLRP3 siRNA were used to downregulate the expression of TLR4 and NLRP3. The expression levels of miR-124, signaling proteins (TLR4, MyD88, and NF-κB p65), inflammasome markers (NLRP3 and IL-1β), and microglial activated markers (CD206, Arg-1, CD86, and iNOS) were measured by qPCR and western blotting. The Pyroptosis rate was assessed using flow cytometry. First, palmitic acid upregulated TLR4/MyD88/NF-κB p65 signaling, increased NLRP3 expression, elevated the Pyroptosis rate, and promoted the microglial proinflammatory response in BV2 cells. Second, the miR-124 mimic and inhibitor separately alleviated and aggravated the effect of palmitic acid on microglial activation and NLRP3 expression. The miR-124 mimic also downregulated TLR4/MyD88/NF-κB p65 signaling. Third, TAK-242 did not affect the expression of miR-124 but simulated the protective effect of the miR-124 mimic on microglial activation and NLRP3 expression. Fourth, NLRP3 siRNA also inhibited the microglial proinflammatory response in BV2 cells. MiR-124 prevented the microglial proinflammatory response through TLR4/MyD88/NF-κB p65/NLRP3 signaling in palmitic acid-treated BV2 cells.

Keywords

High-fat diet; Inflammasome; MiR-124; Microglia; NLRP3; Neuroinflammation.

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