In summary, this study demonstrated that microglia-mediated inflammatory response played essential roles in neuronal apoptosis and IH-associated cognitive decline, and that SENP1 depletion exaggerated microglia-mediated inflammation and subsequently neuronal apoptosis probably by promoting the SUMOylation of PPARγ, thus contributing to the downregulation of PPARγ in hippocampus and IH-related cognitive decline of mice. Here, PPARG is linked to Mental deterioration.