Abstract
Sex is a key biological variable in traumatic brain injury (TBI) and plays a significant role in neuroinflammatory responses. However, the molecular mechanisms contributing to this sexually dimorphic neuroinflammatory response remain elusive. Here we describe a significant and previously unreported tissue enrichment and sex-specific alteration of a set of inflammatory microRNAs (miRNAs) in CD11b+ cells of brain and bone marrow isolated from naïve mice as well as mice subjected to TBI. Our data from naïve mice demonstrated that expression levels of miR-146a-5p and miR-150-5p were relatively higher in brain CD11b+ cells, and that miR-155-5p and miR-223-3p were highly enriched in bone marrow CD11b+ cells. Furthermore, while miR-150-5p and miR-155-5p levels were higher in male brain CD11b+ cells, no significant sexual difference was observed for miR-146a-5p and miR-223-3p. However, TBI resulted in sex-specific differential responses of these miRNAs in brain CD11b+ cells. Specifically, miR-223-3p levels in brain CD11b+ cells were markedly elevated in both sexes in response to TBI at 3 and 24 h, with levels in females being significantly higher than males at 24 h. We then focused on analyzing several miR-223-3p targets and inflammation-related marker genes following injury. Corresponding to the greater elevation of miR-223-3p in females, the miR-223-3p targets, TRAF6 and FBXW7 were significantly reduced in females compared to males. Interestingly, anti-inflammatory genes ARG1 and IL4 were higher in females after TBI than in males. These observations suggest miR-223-3p and other inflammatory responsive miRNAs may play a key role in sex-specific neuroinflammatory response following TBI.
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This work is supported by a Grant (18-8A) from the Kentucky Spinal Cord and Head Injury Research Trust to JES and WXW.
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Study concept and design: JES, WXW, PP; Experimental implementations: PP, WXW, SP, UG; Data acquisition and analysis: PP, WXW; Statistical analysis: PP, WXW; Manuscript preparation: PP, WXW, JES; Manuscript editing and review: JES, WXW, PP, SP, UG.
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All animal procedures used in this study conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the University of Kentucky’s Institutional Animal Care and Use Committee (IACUC protocol no.: 2019-3223).
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Prajapati, P., Wang, WX., Pesina, S.A. et al. Sex-Specific Alterations in Inflammatory MicroRNAs in Mouse Brain and Bone Marrow CD11b+ Cells Following Traumatic Brain Injury. Cell Mol Neurobiol 43, 423–429 (2023). https://doi.org/10.1007/s10571-021-01164-6
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DOI: https://doi.org/10.1007/s10571-021-01164-6