Zinc Deficiency Reduces Neurogenesis Accompanied by Neuronal Apoptosis Through Caspase-dependent and -independent Signaling Pathways

Overview

Journal Neurotox Res

Publisher Springer

Specialty Neurology

Date 2009 Jun 24

PMID 19548052

Citations 34

Authors

Hui-Ling Gao

Wei Zheng

Na Xin

Zhi-Hong Chi

Zhen-Yu Wang

Jie Chen

Zhan-You Wang

Affiliations

Soon will be listed here.

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.

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References

Takeda A, Minami A, Takefuta S, Tochigi M, Oku N . Zinc homeostasis in the brain of adult rats fed zinc-deficient diet. J Neurosci Res. 2001; 63(5):447-52. DOI: 10.1002/1097-4547(20010301)63:5<447::AID-JNR1040>3.0.CO;2-C. View

Takeda A, Yamada K, Tamano H, Fuke S, Kawamura M, Oku N . Hippocampal calcium dyshomeostasis and long-term potentiation in 2-week zinc deficiency. Neurochem Int. 2007; 52(1-2):241-6. DOI: 10.1016/j.neuint.2007.06.021. View

Frederickson C, Koh J, Bush A . The neurobiology of zinc in health and disease. Nat Rev Neurosci. 2005; 6(6):449-62. DOI: 10.1038/nrn1671. View

Gould , Tanapat , Hastings , Shors . Neurogenesis in adulthood: a possible role in learning. Trends Cogn Sci. 1999; 3(5):186-192. DOI: 10.1016/s1364-6613(99)01310-8. View

Chi Z, Wang X, Wang Z, Gao H, Dahlstrom A, Huang L . Zinc transporter 7 is located in the cis-Golgi apparatus of mouse choroid epithelial cells. Neuroreport. 2006; 17(17):1807-11. DOI: 10.1097/01.wnr.0000239968.06438.c5. View

Kesner R, Rogers J . An analysis of independence and interactions of brain substrates that subserve multiple attributes, memory systems, and underlying processes. Neurobiol Learn Mem. 2004; 82(3):199-215. DOI: 10.1016/j.nlm.2004.05.007. View

Kempermann G, Wiskott L, Gage F . Functional significance of adult neurogenesis. Curr Opin Neurobiol. 2004; 14(2):186-91. DOI: 10.1016/j.conb.2004.03.001. View

Takeda A . Zinc homeostasis and functions of zinc in the brain. Biometals. 2002; 14(3-4):343-51. DOI: 10.1023/a:1012982123386. View

Takeda A . Movement of zinc and its functional significance in the brain. Brain Res Brain Res Rev. 2000; 34(3):137-48. DOI: 10.1016/s0165-0173(00)00044-8. View

10.

Shors T, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E . Neurogenesis in the adult is involved in the formation of trace memories. Nature. 2001; 410(6826):372-6. DOI: 10.1038/35066584. View

11.

Treves A, Rolls E . Computational analysis of the role of the hippocampus in memory. Hippocampus. 1994; 4(3):374-91. DOI: 10.1002/hipo.450040319. View

12.

Li Y, Hough C, Frederickson C, Sarvey J . Induction of mossy fiber --> Ca3 long-term potentiation requires translocation of synaptically released Zn2+. J Neurosci. 2001; 21(20):8015-25. PMC: 6763855. View

13.

Halas E, Hunt C, Eberhardt M . Learning and memory disabilities in young adult rats from mildly zinc deficient dams. Physiol Behav. 1986; 37(3):451-8. DOI: 10.1016/0031-9384(86)90205-2. View

14.

Zhang L, Wang X, Stoltenberg M, Danscher G, Huang L, Wang Z . Abundant expression of zinc transporters in the amyloid plaques of Alzheimer's disease brain. Brain Res Bull. 2008; 77(1):55-60. DOI: 10.1016/j.brainresbull.2008.03.014. View

15.

Jessberger S, Romer B, Babu H, Kempermann G . Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells. Exp Neurol. 2005; 196(2):342-51. DOI: 10.1016/j.expneurol.2005.08.010. View

16.

Lu Y, Taverna F, Tu R, Ackerley C, Wang Y, Roder J . Endogenous Zn(2+) is required for the induction of long-term potentiation at rat hippocampal mossy fiber-CA3 synapses. Synapse. 2000; 38(2):187-97. DOI: 10.1002/1098-2396(200011)38:2<187::AID-SYN10>3.0.CO;2-R. View

17.

Ambrogini P, Lattanzi D, Ciuffoli S, Agostini D, Bertini L, Stocchi V . Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus. Brain Res. 2004; 1017(1-2):21-31. DOI: 10.1016/j.brainres.2004.05.039. View

18.

Wang Z, Danscher G, Dahlstrom A, Li J . Zinc transporter 3 and zinc ions in the rodent superior cervical ganglion neurons. Neuroscience. 2003; 120(3):605-16. DOI: 10.1016/s0306-4522(03)00419-6. View

19.

Suh S, Listiack K, Bell B, Chen J, Motamedi M, Silva D . Detection of pathological zinc accumulation in neurons: methods for autopsy, biopsy, and cultured tissue. J Histochem Cytochem. 1999; 47(7):969-72. DOI: 10.1177/002215549904700715. View

20.

Gao H, Xu H, Wang X, Dahlstrom A, Huang L, Wang Z . Expression of zinc transporter ZnT7 in mouse superior cervical ganglion. Auton Neurosci. 2008; 140(1-2):59-65. DOI: 10.1016/j.autneu.2008.04.002. View