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 µg/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.
This is an open access article distributed under the Creative Commons Attribution License
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited