Disruption of the CaMKII/CREB signaling is associated with zinc deficiency-induced learning and memory impairments.
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.
Gao
Hui-Ling
HL
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.
Xu
He
H
Xin
Na
N
Zheng
Wei
W
Chi
Zhi-Hong
ZH
Wang
Zhan-You
ZY
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*
D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D015032:Zinc