Emerging role of miR‐223‐3p in regulating sex dimorphic neuroinflammation and cognitive function in mice following controlled cortical impact

Abstract

AbstractBackgroundNeuroinflammation is a key feature of many neurodegenerative diseases, however its regulation is not well understood. MicroRNAs (miRNAs) are small, non‐coding RNAs that involve in the regulation of many biological and pathological pathways including inflammation. MiR‐223‐3p is macrophage/microglia enriched miRNA that involves in inflammation and immunity. However, the role of miR‐223‐3p in neurodegeneration is unknown.MethodMiR‐223‐3p knockout (KO) and genetic background matched wildtype (WT), female and male young (12‐14‐week) or aged (18‐20‐month) mice were used in the studies. CD11b+ cells were isolated from brain tissues of KO and WT, female and male naïve mice and RT‐qPCR was used to quantify inflammatory markers. Immunofluorescent studies using anti‐IBA1 was used to determine the number of activated microglia in brain sections of aged KO and WT female mice following a CCI. To evaluate the impact of miR‐223‐3p on cognitive and behavior, young (12‐14‐week) or old (18‐20‐month) mice were subjected to CCI followed by a radio arm water maze (RAWM) test (young mice) or Y‐maze test (aged mice) 2 weeks after controlled cortical impact (CCI).ResultOur preliminary studies reveal that deficiency of miR‐223‐3p resulted in a female‐biased elevation of inflammatory transcripts including such as NLRP3, TRAF6, TNFα, NFκB, and ITGAM in brain CD11b+ cells. In addition, immunofluorescent analysis demonstrated that a greater number of IBA1 staining microglia in KO than that of WT mice brains. Furthermore, deficiency of miR‐223‐3p seemed to associate with a deficit in cognitive function in aged female mice following CCI. We also examined the level of CCAAT‐enhancer‐binding protein beta (CEBPβ), an important transcription factor regulating inflammation and a validated target of miR‐223‐3p. Our preliminary data showed that CEBPβ protein was increased in the brain of miR‐223‐3p KO mice brain tissue relative to that of WT.ConclusionOur preliminary data suggest that miR‐223‐3p may regulate a sexually dimorphic neuroinflammation and cognitive function, likely via regulating inflammation transcription factor CEBPβ.