In addition, many studies using mouse models with AD have reported that decreased emotional or social interactions exacerbate AD-related pathologies and cognitive impairment (Pietropaolo et al., 2009; Huang et al., 2011, 2015); however, the application of social interactions in an mouse model with AD decreased histone deacetylase 2 (HDAC2) expression and occupancy of HDAC2 in the promoter region of brain-derived neurotrophic factor (BDNF) exon IV, resulting in upregulated BDNF expression in the hippocampus region through increased acetylation of H3K9 and H4K12 histones. This evidence concerns the gene BDNF and Cognitive impairment.