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.