The impact of subchronic low-dose exposure to nonylphenol on depression-like behaviors in high-sucrose and high-fat diet induced rats

Objective: We investigated the impact of subchronic low-dose exposure to nonylphenol (NP) on depression-like behaviors and synaptic morphological plasticity in the context of a high-sucrose/high-fat diet in rats. Methods: Male Sprague Dawley (SD) rats were randomly divided into 8 groups (n = 10 per group), as follows: rats fed a normal-diet (ND), as the control (C-ND); rats fed a normal diet and gavaged with NP at a dose of 0.02 mg/kg/day (NP-L-ND), 0.2 mg/kg/day (NP-M-ND) or 2 mg/kg/day (NP-H-ND); rats fed a high-sucrose/ high-fat diet (HSHFD), as the HSHFD control (C-HSHFD); rats fed a HSHFD and gavaged with NP at a dose of 0.02 mg/kg/day (NP-L-HSHFD), 0.2 mg/kg/day (NP-M-HSHFD) or 2 mg/kg/day (NP-H-HSHFD). Elevated plus maze was used to evaluate anxiety behavior. Open field test was used to evaluate locomotor activity. Cyclooxygenase-2 expression in hippocampal tissue was measured by immunohistochemistry. The ultrastructure of hippocampal mitochondria and the synaptic plasticity were observed by transmission electron microscopy. Results: Significant interactions between HSHFD and NP-H were observed, reflected by the time spent exploring the open arms, time spent in the center area, distance traveled in the center area and total distance traveled (p < 0.05). Exposure to NP-H-HSHFD resulted in swelling of the mitochondria, associated with an increased number of disordered and partially disrupted cristae compared with the control group. Synaptic interface curvatures and postsynaptic density thickness decreased as the NP dose increased among the treatment groups. Co exposure to HSHFD and NP showed an increase in synaptic cleft width compared with the HSHFD-only and NP only exposure groups (p < 0.05). COX-2 expression and integral optical density value increased as the NP dose increased among the NP treatment groups (p < 0.05). Conclusion: Subchronic low-dose exposure to NP might induce alterations in depression-like behaviors, synaptic morphological plasticity and COX-2 expression in the hippocampus. Co-exposure to NP and HSHFD had significantly more dissimilarities.