title: The alterations of Ca2+/calmodulin/CaMKII/CaV1.2 signaling in experimental models of Alzheimer's disease and vascular dementia.
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.
authors: Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China.
authors: Dongyu
authors: D
authors: Min
authors: Feng
authors: F
authors: Guo
authors: Shu
authors: S
authors: Zhu
authors: Xiaoxue
authors: X
authors: Xu
authors: Xiaoyuan
authors: X
authors: Mao
authors: Yonggang
authors: Y
authors: Cao
authors: Xintong
authors: X
authors: Lv
authors: Qinghua
authors: Q
authors: Gao
authors: Lei
authors: L
authors: Wang
authors: Tianbao
authors: T
authors: Chen
authors: Chris
authors: C
authors: Shaw
authors: Liying
authors: L
authors: Hao
authors: Jiqun
authors: J
authors: Cai
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D015140:Dementia, Vascular / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D005849:Gerbillinae; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C); D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium