Oxytocin alleviates cognitive and memory impairments by decreasing hippocampal microglial activation and synaptic defects via OXTR/ERK/STAT3 pathway in a mouse model of sepsis-associated encephalopathy.
Level 5 - mechanism / opinion, no new human data
Animal model and in vitro laboratory study
PubMed 37648002 · doi:10.1016/j.bbi.2023.08.023
What was done
Sepsis-associated encephalopathy (SAE) was induced in adult male C57BL/6J mice via cecal ligation and perforation (CLP) surgery. Mice received post-surgical intranasal oxytocin (OXT). The authors evaluated clinical scores, survival rates, cognitive and memory behaviors, and hippocampal neuronal and synaptic functions. Cultured microglia treated with lipopolysaccharide (LPS) were used to measure cytokine release and phagocytosis. Signaling pathways and receptor specificity were evaluated using RNA sequencing and the OXTR antagonist L-368,899.
What was found
CLP surgery decreased hippocampal OXT levels and increased OXTR expression at around 24 hours. Intranasal OXT administration increased survival rates, reduced cognitive and memory dysfunction, and restored hippocampal synaptic function and neuronal activity. Administration of the OXTR antagonist L-368,899 blocked these effects. In LPS-treated microglia, OXT reduced phagocytosis and inflammatory cytokine release via the OXTR-ERK-STAT3 pathway. The abstract reported no exact numerical values, percentages, or effect sizes.
Why it matters
This paper identifies oxytocin signaling dysfunction as a feature of sepsis-associated encephalopathy in mice and suggests that intranasal oxytocin may reduce neuroinflammation and preserve cognitive function.
Limits
The study is restricted to a rodent model and in vitro microglial culture, so clinical efficacy in humans is unknown. No exact sample sizes, survival rates, or quantitative statistical results were reported in the abstract. Only male mice were tested, preventing evaluation of sex differences.
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