title: Disruption of the CaMKII/CREB signaling is associated with zinc deficiency-induced learning and memory impairments.
abstract: 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.
authors.affiliation: Key Lab of Cell Biology of Ministry of Education of China, China Medical University, Bei-Er Road 92, Shenyang 110001, People's Republic of China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Gao
authors.forename: He
authors.initials: H
authors.lastname: Xu
authors.forename: Na
authors.initials: N
authors.lastname: Xin
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chi
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors* / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology; D007858:Learning / Q000502:physiology*; D008569:Memory Disorders / Q000201:enzymology*; D051379:Mice; D011897:Random Allocation; D015398:Signal Transduction / Q000502:physiology*; D015032:Zinc / Q000172:deficiency*
chemical_list: D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D015032:Zinc