title: Disturbance of intracellular calcium homeostasis and CaMKII/CREB signaling is associated with learning and memory impairments induced by chronic aluminum exposure.
abstract: Aluminum-induced neuronal injury has been implicated in various neurodegenerative disorders. However, the underlying mechanism involved in this pathogenesis still remains unknown. Our present findings demonstrated that chronic aluminum exposure resulted in spatial learning impairment and significantly increased intracellular calcium level in the hippocampus of rats. Examination of the associated protein molecules essential for induction and maintenance of long-term potentiation revealed that aluminum exposure could increase the expression level of calmodulin (CaM), but the expression levels of CaM-dependent protein kinase II (CaMKII), and phosphorylated cAMP-responsive element binding protein (CREB) were significantly reduced, whereas the total protein levels of CaMKII and CREB did not change in the aluminum-treated hippocampus. Thus, we provide a previously unrecognized mechanism whereby chronic aluminum exposure impairs hippocampal learning and memory, at least in part, through disruption of intracellular calcium homeostasis and CaM/CaMKII/CREB signaling pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, No. 92 Bei'er Road, Heping District, Shenyang, 110001, People's Republic of China, cmuwb@hotmail.com.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.forename: Jiuhan
authors.initials: J
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Yifu
authors.initials: Y
authors.lastname: Guan
mesh_terms: D000535:Aluminum / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006706:Homeostasis / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology
chemical_list: C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D000535:Aluminum; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium