Obesogenic diet-induced insulin-resistant rats develop neurobehavioral and memory deficits following bisphenol-A and cadmium co-exposure

Abstract

Objectives Obesogenic high-fat diets (HFD) have been widely implicated in the etiology of dementia-related neuropathologies through the disruption of brain insulin signaling. Likewise, exposure to environmental toxicants has been associated with various neurodegenerative symptoms attributed to their oxidative stress-mediated neurotoxicity. Thus, this study aims to investigate the effects of exposure to the environmental toxicants, bisphenol-A (BPA) and cadmium (Cd), on the exploratory instinct and spatial awareness memory of HFD-induced insulin-resistant adult Wistar rats. Material and Methods Twenty-five adult Wistar rats were randomly assigned to five groups (A–E; n = 5) and treated as follows: A: normal saline; B: 40 mg/kg.bw CdCl 2 +HFD+Suc; C: 40 mg/kg.bw BPA+HFD+Suc; D: 40 mg/kg.bw BPA+ 40 mg/kg.bw CdCl 2 +HFD+Suc; E: HFD+Suc, orally for 56 days. Rats were subjected to the Y-maze behavioral test for spatial awareness and learning memory, and the respective trials were recorded as measures of short-term memory and spatial awareness. On the last day of the experiment, brains were excised, the hippocampus was dissected from each group, and samples were processed for H&E histological investigation. Results Results from this study revealed that BPA and Cd impaired exploratory instincts and spatial awareness of insulin-resistant rats by significantly reducing their exploration of the Y-maze. The hippocampus of exposed rats also revealed neurodegenerative-like changes in histoarchitectural studies with extensive nuclear condensation. Conclusion Histomorphological and behavioral evidence from this study suggests that exposure to oxidative stress-inducing and insulin-signaling perturbing chemicals cause deficits in cognitive and short-term memory.