Modulation of the chelatable Zn pool in the brain by diethyldithiocarbamate is associated with behavioral impairment in adult zebrafish Public Deposited

http://ir.library.oregonstate.edu/concern/articles/w0892g30x

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  • The study of the effects of diethyldithiocarbamate (DEDTC) in some diseases is in focus for many years. However, DEDTC is a metal chelator that can present neurotoxicity as side effects. Here we investigate the effect of DEDTC on brain Zinc (Zn) content and behavior. To address this issue we used adult zebrafish exposed to different concentrations of DEDTC. The animal’s behavioral parameters were evaluated during the exposure of DEDTC (0.2, 1, 5 mM in home tank water) for 1h. At the end of exposure period, the brain levels of DEDTC were measured. The analysis of reactive Zn content in different regions of the brain and in glutamatergic neurons and radial glial cells were performed using histochemical and immunocytochemical techniques, respectively. We also measured the activity of a Zn-dependent enzyme, δ-aminolevulinate dehydratase (δ-ALA-D). We found that DEDTC exposure at 1 and 5 mM induced seizure-like behavior in the zebrafish and death at 5 mM. DEDTC in the zebrafish brain was detected with exposure of 1 and 5 mM (above 100 mg.kg⁻¹ tissue). The reactive Zn was reduced in glutamatergic neurons after 1 and 5 mM DEDTC exposure in radial glial cells after 0.2 and 5 mM. No changes in brain δ-ALA-D activity were detected. Our results showed that DEDTC exposure can accumulate in the brain, leading to impairments in neural behavior and in the homeostasis of reactive Zn in the brain.
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  • Braga, M. M., Silva, E. S., Rico, E. P., Pettenuzzo, L. F., Oliveira, D. L., Dias, R. D., ... & Rosemberg, D. B. (2015). Modulation of the chelatable Zn pool in the brain by diethyldithiocarbamate is associated with behavioral impairment in adult zebrafish. Toxicology Research, 4(2), 317-325. doi:10.1039/C4TX00111G
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