Disruption of the CaMKII/CREB Signaling is Associated with Zinc Deficiency-Induced Learning and Memory Impairments

作者：Gao Hui Ling; Xu He; Xin Na; Zheng Wei; Chi Zhi Hong; Wang Zhan You^*

来源：Neurotoxicity Research, 2011, 19(4): 584-591.

DOI：10.1007/s12640-010-9206-y

• Calmodulin-dependent protein kinase II
• cAMP-responsive element binding protein
• Long-term potentiation
• Morris water maze
• Neurogranin

Many studies have shown that zinc deficiency not only retards growth, but also affects several brain functions, including learning and memory. However, the underlying mechanism of impaired hippocampus-dependent learning and memory under zinc deficiency is poorly understood. In this study, young mice were fed a zinc-deficient diet (0.85 ppm) for 5 weeks. Morris water maze result showed that zinc deficiency results in spatial learning impairment. We then examined whether zinc depletion-induced learning and memory defects are associated with changes in signaling molecules essential for the expression of long-term potentiation. Immunoblot results showed that the protein levels of calmodulin (CaM), phosphorylated 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 zinc-deficient hippocampus. Thus, we provide a previously unrecognized mechanism whereby zinc deficiency impairs hippocampal learning and memory, at least in part, through disruption of the CaM/CaMKII/CREB signaling pathway.

• 出版日期2011-5
• 单位中国医科大学