Neurobehavioral impairments from chromium exposure: Insights from a zebrafish model and drug validation

Abstract

We have developed a zebrafish model to explore the alterations in neurobehaviors resulting from both acute and chronic exposure to chromium (Cr). Zebrafish exposed to half (HC group: 19.7 mg/L) and a quarter (LC group: 9.85 mg/L) of the LD50 concentration of Cr for a span of 2 weeks exhibited aberrant locomotion, heightened anxiety, cognitive impairment, and reduced aggression - hallmark traits reminiscent of an Alzheimer's Disease (AD)-like syndrome. Furthermore, zebrafish exposed to an environmentally relevant concentration of Cr (EC group: 100 μg/L) for an extended period of 9 weeks exhibited behaviors comparable to those observed in the HC group. Moreover, the study investigated the neuroprotective effects of donepezil (Don), galantamine (Gal) and resveratrol (Res) drugs in response to neurobehavioral impairments induced by Cr (VI) exposure in zebrafish. Don and Res effectively protect the zebrafish from Cr (VI)-induced anxiety, and memory impairment. Furthermore, Cr (VI) exposure induced heightened oxidative stress while simultaneously diminishing antioxidant enzyme levels. Remarkably, these effects were counteracted in the drug-treated groups. Likewise, exposure to Cr (VI) led to an increase in the expression of genes linked to AD and neuroinflammation. Nevertheless, drug treatment reversed this effect in Cr (VI)-exposed fish. The results of our study highlight the potentials of zebrafish model in demonstrating neurobehavioral impairments induced by Cr (VI), thereby paving the way for its utilization in vivo neurobehaviors investigations and pharmaceutical screening.