CREB1 and Mental deterioration: Accordingly, a large number of previous studies demonstrated that targeted activation of H3R in neurons resulted in an accelerated cognitive decline and aggravated Aβ-induced neuronal perturbation in β-amyloid precursor protein (APP) transgenic mice, accompanied by progressive loss of cholinergic neurons and destructive signaling pathways involving cAMP/CREB and AKT/GSK3β cascades (Bhowmik et al., 2014; Bardgett et al., 2011; Bitner et al., 2011).