The alterations of Ca²⁺/calmodulin/CaMKII/Ca_V1.2 signaling in experimental models of Alzheimer's disease and vascular dementia

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• 作者：Dongyu Min^a ; ^b ; ¹ ; Feng Guo^a ; ¹ ; Shu Zhu^c ; Xiaoxue Xu^d ; Xiaoyuan Mao^a ; Yonggang Cao^a ; Xintong Lv^a ; Qinghua Gao^a ; Lei Wang^e ; Tianbao Chen^e ; Chris Shaw^e ; Liying Hao^a ; Jiqun Cai^a ; ^{jqcai@mail.cmu.edu.cn}
• 关键词：Alzheimer's disease ; Vascular dementia ; CaV1.2 ; CaMKII ; Calmodulin
• 刊名：Neuroscience Letters
• 出版年：2013
• 出版时间：22 March, 2013
• 年：2013
• 卷：538
• 期：Complete
• 页码：60-65
• 全文大小：1136 K

文摘

The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD). The alterations of Ca²⁺/calmodulin/CaMKII/Ca_V1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of Ca_V1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/Ca_V1.2 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 A¦Â_1-42. The expression of Ca_V1.2 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 Ca_V1.2 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¦Â_1-42. Collectively, our results suggest that the alterations in Ca_V1.2, 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.