| First Author | Choi BY | Year | 2017 |
| Journal | Int J Mol Sci | Volume | 18 |
| Issue | 10 | PubMed ID | 29048371 |
| Mgi Jnum | J:272789 | Mgi Id | MGI:6282413 |
| Doi | 10.3390/ijms18102189 | Citation | Choi BY, et al. (2017) ZnT3 Gene Deletion Reduces Colchicine-Induced Dentate Granule Cell Degeneration. Int J Mol Sci 18(10):2189 |
| abstractText | Our previous study demonstrated that colchicine-induced dentate granule cell death is caused by blocking axonal flow and the accumulation of intracellular zinc. Zinc is concentrated in the synaptic vesicles via zinc transporter 3 (ZnT3), which facilitates zinc transport from the cytosol into the synaptic vesicles. The aim of the present study was to identify the role of ZnT3 gene deletion on colchicine-induced dentate granule cell death. The present study used young (3-5 months) mice of the wild-type (WT) or the ZnT3(-)(/)(-) genotype. Colchicine (10 microg/kg) was injected into the hippocampus, and then brain sections were evaluated 12 or 24 h later. Cell death was evaluated by Fluoro-Jade B; oxidative stress was analyzed by 4-hydroxy-2-nonenal; and dendritic damage was detected by microtubule-associated protein 2. Zinc accumulation was detected by N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining. Here, we found that ZnT3(-)(/)(-) reduced the number of degenerating cells after colchicine injection. The ZnT3(-)(/)(-)-mediated inhibition of cell death was accompanied by suppression of oxidative injury, dendritic damage and zinc accumulation. In addition, ZnT3(-)(/)(-) mice showed more glutathione content than WT mice and inhibited neuronal glutathione depletion by colchicine. These findings suggest that increased neuronal glutathione by ZnT3 gene deletion prevents colchicine-induced dentate granule cell death. |
