Moreover, ERβ activation reduces weight gain induced by high-fat diets (Foryst-Ludwig et al., 2008), enhances hippocampal memory (Boulware et al., 2013; Jacome et al., 2010; Pereira et al., 2014; Walf et al., 2008), and reduces anxiety-and depression-like behaviors in OVX rodents (Lagunas et al., 2010; Li et al., 2014; Lund et al., 2005; Oyola et al., 2012; Walf and Frye, 2005a, 2007). Here, ESR2 is linked to major depressive disorder.