Sepsis, defined as a dysregulated host immune response to infection, is a common and dangerous clinical syndrome. The excessive host inflammatory response can induce immediate and persistent cognitivedecline, which can be worse in older individuals. Sex-specific differences in the outcome of infectiousdiseases and sepsis appear to favor females. We employed a murine model to examine the influence of ageand sex on the brain's microRNA (miR) response following sepsis. Young and old mice of both sexesunderwent cecal ligation and puncture (CLP) with daily restraint stress. Expression of hippocampal miR wasexamined in age and sex-atched controls at 1 and 4 days post-CLP. Few miR were modified in a similarmanner across age or sex and these few miR were generally associated with neuroprotection againstinflammation. Similar to previous work examining transcription, young females exhibited a better recoveryof the miR profile from day 1 to day 4, relative to young males and old females. For young males and allfemale groups, the initial response mainly involved a decrease in miR expression. In contrast, old malesexhibited only upregulated miR on day 1 and day 4 and many of the miR upregulated on day 1 and day 4were linked to neurodegeneration, increased neuroinflammation, and cognitive impairment. The resultsemphasize age and sex differences in epigenetic mechanisms that likely contribute to susceptibility orresilience to cognitive impairment due to sepsis
CITATION STYLE
Rani, A., Barter, J., Kumar, A., Stortz, J. A., Hollen, M., Nacionales, D., … Foster, T. C. (2022). Influence of age and sex on microRNA response and recovery in the hippocampus following sepsis. Aging, 14(2), 728–746. https://doi.org/10.18632/aging.203868
Mendeley helps you to discover research relevant for your work.