Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China.
Neurosci Lett. 2013 Mar 22;538:60-5. doi: 10.1016/j.neulet.2013.02.001. Epub 2013 Feb 8.
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.
两种主要的痴呆形式是阿尔茨海默病（AD）和血管性痴呆（VD）。AD 和 VD 中 Ca(2+)/钙调蛋白/CaMKII/CaV1.2 信号的改变尚未得到充分阐明。在这里，我们通过 Western blot 分析证明了 APP/PS1 小鼠和 VD 沙土鼠海马中 CaV1.2、钙调蛋白、p-CaMKII、p-CREB 和 BDNF 蛋白水平的变化，以及通过双标记免疫荧光检测 p-CaMKII/CaV1.2 的共定位。此外，还在经 Aβ1-42 处理的培养神经元中检查了这些蛋白质的表达和细胞内钙水平。CaV1.2 蛋白的表达在 VD 沙土鼠和培养神经元中增加，但在 APP/PS1 小鼠中减少；钙调蛋白蛋白的表达在 APP/PS1 小鼠和 VD 沙土鼠中增加；AD 和 VD 模型中 p-CaMKII、p-CREB 和 BDNF 蛋白水平降低。p-CaMKII 和 CaV1.2 共定位的神经元数量在两个模型的 CA1 和 CA3 区减少。用 Aβ1-42 处理的培养神经元中的细胞内钙增加。总的来说，我们的结果表明，CaV1.2、钙调蛋白、p-CaMKII、p-CREB 和 BDNF 的改变可以反映 AD 和 VD 模型中记忆和认知损伤的参与。
