SOCS3 Suppression Is Associated with Hippocampal Inflammation in a Mouse Model of Intermittent Hypoxia

Background/Objectives: Intermittent hypoxia (IH), a feature of obstructive sleep apnea (OSA), is associated with hippocampal inflammation and cognitive dysfunction. We examined SOCS3 expression and a possible MALAT1/EZH2/H3K27me3 regulatory relationship in a mouse IH model and BV2 cells. Methods: C57BL/6J mice were exposed to IH for 4 weeks, followed by Morris water maze testing and analysis of hippocampal tissue. BV2 cells were exposed to IH and used for transfection, RNA immunoprecipitation, and chromatin immunoprecipitation experiments. Results: In mice, IH was associated with poorer water maze performance, lower hippocampal SOCS3, and higher levels of inflammatory markers, MALAT1, and H3K27me3. Similar molecular changes were observed in BV2 cells. SOCS3 overexpression reduced TRAF6, total NF-κB p65, TNF-α, and IL-1β protein levels in BV2 cells. MALAT1 was enriched by EZH2 immunoprecipitation, H3K27me3 was enriched at the SOCS3 promoter, and MALAT1 knockdown reduced total H3K27me3 while increasing SOCS3 protein. Conclusions: These findings associate reduced SOCS3 with hippocampal inflammation after IH and support further investigation of MALAT1 and EZH2 in its regulation. The cellular source of the in vivo inflammatory markers and the causal role of EZH2 require direct testing.