Referenced in: none

Automatically associated channels: Cav1.2

Title: The alterations of Ca2+/calmodulin/CaMKII/CaV1.2 signaling in experimental models of Alzheimer's disease and vascular dementia.

Authors: Dongyu Min, Feng Guo, Shu Zhu, Xiaoxue Xu, Xiaoyuan Mao, Yonggang Cao, Xintong Lv, Qinghua Gao, Lei Wang, Tianbao Chen, Chris Shaw, Liying Hao, Jiqun Cai

Journal, date & volume: Neurosci. Lett., 2013 Mar 22 , 538, 60-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23403102

Abstract
The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD). The alterations of Ca(2+)/calmodulin/CaMKII/CaV1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/CaV1.2 by double-labeling immunofluorescence in the hippocampus of APP/PS1 mice and VD gerbils. Additionally, expression of these proteins and intracellular calcium levels were examined in cultured neurons treated with Aβ1-42. The expression of CaV1.2 protein was increased in VD gerbils and in cultured neurons but decreased in APP/PS1 mice; the expression of calmodulin protein was increased in APP/PS1 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 CaV1.2 were co-localized, was decreased in the CA1 and CA3 regions in two models. Intracellular calcium was increased in the cultured neurons treated with Aβ1-42. Collectively, our results suggest that the alterations in CaV1.2, 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.