The alterations of Ca2+/calmodulin/CaMKII/Cav1.2 signaling in experimental models of Alzheimer's disease and vascular dementia

The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD). The alterations of Ca2+/calmodulin/CaMKII/Ca(v)1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of Ca(v)1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/Ca(v)1.2 by double-labeling immunofluorescence in the hippocampus of APP/PSI mice and VD gerbils. Additionally, expression of these proteins and intracellular calcium levels were examined in cultured neurons treated with A beta(1-42). The expression of Ca(v)1.2 protein was increased in VD gerbils and in cultured neurons but decreased in APP/PSI mice; the expression of calmodulin protein was increased in APP/PSI mice and VD gerbils; levels of p-CaMKII, p-CREB and BDNF proteins were decreased in AD and VD models. The number of neurons in which p-CaMKII and Ca(v)1.2 were co-localized, was decreased in the CA1 and CA3 regions in two models. Intracellular calcium was increased in the cultured neurons treated with A beta(1-42). Collectively, our results suggest that the alterations in Ca(v)1.2, calmodulin, p-CaMKII, p-CREB and BDNF can be reflective of an involvement in the impairment in memory and cognition in AD and VD models. (C) 2013 Elsevier Ireland Ltd. All rights reserved.