Sex differences in the neuroinflammatory signaling pathway: Effect of miRNAs on fatty acid synthesis in microglia

Studies have shown that Alzheimer’s disease is more prevalent and severe in women than men. This could be due to the different gene and protein expression in the microglia, the brain’s primary immune cells. In this study, we analyzed microglial microRNAs from the hippocampi of adult male and female mice and identified 30 miRNAs that were expressed differently in male and female mice. The target genes of the male-enriched miRNAs belong to the fatty acid biosynthesis and metabolism pathways. As sex hormones contribute to sex differences, we investigated whether testosterone regulates the fatty acid biosynthesis pathway in the mouse microglial cell line MG6. Testosterone reduced the expression levels of fatty acid synthase, which in turn suppresses the NF-κB inflammatory signaling pathway. This suggests that testosterone, through the upregulation of specific miRNAs, plays a crucial role in suppressing inflammatory responses in male microglia, which could explain the lower susceptibility of men towards Alzheimer’s disease. Hippocampi were isolated from 8-month-old male and female mice (five mice per group) and pooled to generate one sample per sex.