title: Zinc deficiency reduces neurogenesis accompanied by neuronal apoptosis through caspase-dependent and -independent signaling pathways.
abstract: Dietary zinc deficiency may affect zinc homeostasis in the brain and lead to reductions of neurogenesis and neuronal survival. However, the mechanisms responsible for the effects of zinc deficiency on hippocampal neurogenesis and neuronal death remain obscure. In the present study, young CD-1 mice were fed with zinc-deficient diet (0.85 ppm) for 5 weeks. The vesicular zinc was reduced at CA1 and CA3 regions of the hippocampus in zinc-deficient mice. The significant decreased zinc ions was associated with a reduction in proliferating cells labeled with bromo-deoxyuridine (BrdU) and immature neurons labeled with doublecortin (DCX) immunoreactivity in the dentate gyrus of the hippocampus. The processes of DCX-positive neurons were shortened, and flexuously went through into the granular cell layer in zinc-deficient hippocampus. There was also a conspicuous increase in the number of TUNEL-positive cells in the hippocampus after zinc-deficient diet treatment. Meanwhile, the apoptosis proteins, including Fas, Fas ligand (FasL), apoptosis inducing factor (AIF), and caspase-3, were significantly activated in zinc-deficient mouse hippocampus. These data suggest that chronic treatment with zinc-deficient diet results in reduction in hippocampal neurogenesis and increases neuronal apoptosis, indicating that zinc deficiency is associated with destroying structural plasticity in the hippocampus.
authors: Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110001, People's Republic of China.
authors: Hui-Ling
authors: HL
authors: Gao
authors: Wei
authors: W
authors: Zheng
authors: Na
authors: N
authors: Xin
authors: Zhi-Hong
authors: ZH
authors: Chi
authors: Zhen-Yu
authors: ZY
authors: Wang
authors: Jie
authors: J
authors: Chen
authors: Zhan-You
authors: ZY
authors: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D053222:Fas Ligand Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000172:deficiency*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D019014:fas Receptor; D053148:Caspase 3; D020169:Caspases; D001973:Bromodeoxyuridine; D015032:Zinc