Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Is
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ORIGINAL PAPER
Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post‑stroke Social Isolation Anik Banerjee1 · Anil K. Chokkalla2,3 · Julia J. Shi4 · Juneyoung Lee1 · Venugopal Reddy Venna1 · Raghu Vemuganti2,3,5 · Louise D. McCullough1 Received: 18 August 2020 / Accepted: 8 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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, miR376c-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. Keywords Stroke · Social isolation · Aging · miRNAs · Sex differences · Biomarkers
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12017-020-08622-2) contains supplementary material, which is available to authorized users. * Louise D. McCullough [email protected] 1
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
2
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
3
Cellular and Molecular Pathology Program, University of Wisconsin, Madison, WI, USA
4
Department of Kinesiology, Rice University, Houston, TX 77005, USA
5
William S. Middleton Veterans Administration Hospital, Madison, WI, USA
Social isolation (SI) is a major cause of mental and psych
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