Ovariectomy experiments in animals have demonstrated that the decreased levels of E2 activate NF-κB signaling pathway in microglia, converting microglia from the M2 subtype to the M1 subtype and resulting in the production and secretion of large amounts of inflammatory cytokines such as TNF-α, IL-1β and IL-6, which leads to cognitive impairment and depressive behavior [45, 46]. This evidence concerns the gene NFKB1 and Cognitive impairment.