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• W4385702014 abstract "Millions of sepsis survivors annually face neuropsychiatric sequelae of their illness. Corticosteroids are frequently administered in sepsis, and their use improves neuropsychiatric outcomes, but the mechanisms are unknown. In light of prior work showing persistent inflammation in sepsis survivors, we hypothesized that short-term corticosteroid treatment during illness would reverse the long-term impact of sepsis on inflammatory gene expression in the hippocampus and rescue associated changes to affective behaviors. Male and female mice underwent cecal ligation and puncture (CLP) or a sham surgery to induce acute infection and were treated for 5 days with corticosterone or vehicle. Starting 2 weeks after the surgery, we performed functional phenotyping in the survivor mice followed by hippocampal RNA-sequencing to identify underlying mechanisms. Long-term CLP survivors exhibited anxiety-like behavior, increased central hypothalamic-pituitary-adrenal (HPA) axis activity, and persistent systemic and neuro-inflammation. Corticosterone treatment during illness did not reverse anxiety-like behavior or inflammation in survivors. Instead, corticosterone treatment impaired object memory and increased active coping behavior in females. History of corticosterone treatment influenced the expression of more than 10% of detectable transcripts in dorsal and ventral hippocampus, including a coordinated downregulation of activity-dependent genes. Corticosterone treatment during sepsis impaired memory formation in survivors and caused a lasting decrease in hippocampal neural activity, which could underlie its effect on memory. Future studies should focus on how this lasting effect of corticosteroid treatment on hippocampal activity and memory translates into improved neuropsychiatric outcomes in human sepsis survivors." @default.
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• W4385702014 date "2023-08-01" @default.
• W4385702014 modified "2023-10-17" @default.
• W4385702014 title "Corticosteroid Treatment During Sepsis Alters Hippocampal Function in Male and Female Survivors" @default.
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• W4385702014 doi "https://doi.org/10.1016/j.bpsgos.2023.08.001" @default.
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