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

Abstract

The study of the effects of diethyldithiocarbamate (DEDTC) in some diseases has been in focus for many years. However, DEDTC is a metal chelator that can present neurotoxicity as side effect. Here we investigate the effect of DEDTC on the 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 exposure to DEDTC (0.2, 1, 5 mM in home tank water) for 1 h. At the end of the exposure period, the brain levels of DEDTC were measured. The analysis of the reactive Zn content in different regions of the brain and in glutamatergic neurons and radial glial cells was 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 to 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. No changes in the brain δ-ALA-D activity were detected. Our results showed that DEDTC can accumulate in the brain, leading to impairment in neural behavior and in the homeostasis of reactive Zn in the brain.