Maternal diet enriched with African walnuts confers neurodevelopmental resilience to MnCl2-induced neurotoxic cascades in rats

Abstract

Background: Early experiences at critical milestones significantly impact neurocognitive outcomes by altering brain development. Such issues can affect children’s academic achievement, disturb their behaviour, lower their quality of life, and raise their risk of derangement in adulthood. These problems are linked to many possible neurotoxicants, including high ambient manganese (Mn) exposure. Walnuts possess high levels of ω-3 fatty acids and a high content of potent phytochemicals, all of which play an essential role in brain health. This present study explored the ability of a maternal walnut-enriched diet (WED) to protect against MnCl2-induced developmental neurotoxicity in utero vis-à-vis early postnatal stages in rats. Dams were exposed to diet and Mn treatment during gestation and/or preweaning periods. At the onset of adolescence (~postnatal day 28), offspring of dams were examined on the Y-maze and elevated-plus maze to evaluate working memory and anxiety levels. After euthanasia, cortical and hippocampal tissues were harvested for subsequent analyses by histology, histochemistry, PCR, and spectrophotometry methods. All data were analyzed using One-way ANOVA followed by Tukey’s test for multiple comparisons. Significance was set at p<0.05. Results: Offspring of dams treated with MnCl2 exhibited a significant reduction in working memory and a loss of emotional stability, which was restored by WED; Mn aberrations in histomorphology of the PFC and hippocampus were abated by WED; dysregulation in gene expression of DNMT3A, H2Ax, BDNF, and OPA1 was prevented by developmental WED; upregulated levels of pro-inflammatory cytokines which correlated with MnCl2 exposure was significantly reduced by walnut supplementation and; finally, accompanied perturbation of the cholinergic system (AChE) by MnCl2 was significantly counteracted by WED. Conclusion: Our data suggest that WED intervened and forestalled deficits in behaviour, structural alterations, and functional dysregulation arising from manganese neurotoxicity in developing rats.