Abstract
Social isolation (SI) increases ischemic injury and significantly delays recovery after experimental stroke. Changes in circulating microRNAs (miRNAs) have been implicated in several neurological disorders, including stroke. However, potential biomarkers to elucidate the mechanisms that underlie the detrimental effects of post-stroke isolation are unknown. Aged C57BL/6 male and female mice (18–20 months) were subjected to a 60-min middle cerebral artery occlusion followed by reperfusion and were assigned to either isolation (SI) or continued pair housing (PH) immediately after stroke. On day 15, mice were sacrificed, and plasma samples were collected for miRNAome analysis. Top candidate miRNAs and their biological functions were identified using integrated bioinformatics. The miRNAome analysis revealed a total of 21 differentially expressed miRNAs across both sexes with fold change of 3 or higher. Within the female cohort, miR-206-3p, -376a-3p, -34b-5p, -133a-5p, -466f, and -671-3p were highly altered relative to the PH housing condition. Similarly in males, miR-376c-3p, -181d-5p, -712-5p, -186-5p, -21a-3p, -30d-3p, -495-3p, -669c-5p, -335-5p, -429-3p, -31-3p, and -217-5p were identified. Following Kyoto Encyclopedia of Genes and Genomes analysis, the identified miRNAs effected distinct subset of pathways within sexes. Interactional network analysis revealed miR-495-3p (male) and miR-34b-5p (female) as pivotal nodes that targeted the largest subset of genes. We identified several sex-specific miRNAs as candidate biomarkers for post-stroke SI in aged male and female mice. Additionally, these results suggest that there is potential to use plasma-based circulating miRNAs as a source of novel biomarkers to identify biological pathways involved in post-stroke SI.
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All data and supporting material details of this study are available from the corresponding or first author of the article on reasonable request.
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Funding
This study was supported by grants from the NIH/NINDS, NSO55215 and 1R01NS096493 (to L.D.M.), RO1NS099531 and RO1NS101960 (to R.V.), an award from the American Heart Association and the American Brain Foundation 19POST34410076 (to J.L.), the American Heart Association grants 15SDG23250025 (to V.R.V.), and AHA-Student Scholarship in Cerebrovascular Disease and Stroke (to A.B.).
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AB, VRV, RV, and LDM designed the experiments for the study and wrote the manuscript. AB, AKC, JJS, JL, and VRV performed the experiments and analyzed the data.
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Banerjee, A., Chokkalla, A.K., Shi, J.J. et al. Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Isolation. Neuromol Med 23, 305–314 (2021). https://doi.org/10.1007/s12017-020-08622-2
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DOI: https://doi.org/10.1007/s12017-020-08622-2