Neurobehavioral Responses of Rats Exposed to Low-Concentration Hexavalent Chromium [Cr(VI)] in Drinking Water Combined with a High-Fat Diet

Hexavalent chromium [Cr(VI)] is an established human carcinogen and was identified as the top chemical hazard in U.S. drinking water. Cr(VI) exposure has been associated with adverse neurological outcomes, while high-fat diet consumption is linked to cognitive impairment and neurodegenerative disease. However, limited evidence exists regarding their combined effects on brain health. This study investigated neurobehavioral changes and brain metal concentrations in young rats exposed to low concentrations of Cr(VI) in drinking water (0.05 mg/L or 0.1 mg/L) while fed a normal-fat or high-fat diet for 90 days. Cr(VI) exposure impaired grip strength in rats, while a high-fat diet attenuated this effect. Co-exposure to Cr(VI) with a high-fat diet reduced exploratory behavior and motor function, increased anxiety, and impaired spatial memory while also decreasing overall activity. Both sociability and social novelty preference were altered by the combined exposure in rats. Notably, Cr(VI) with high-fat diet co-exposure induced sex-specific behavioral changes. High-fat diet affected Cr brain accumulation, and Cr(VI) exposure and high-fat diet disrupted essential metal homeostasis in rat brains with sex differences. Jointly, the results suggest combined exposure to Cr(VI) and a high-fat diet may increase the risk of adverse neurological outcomes.