Inhibitory Effects of Bisphenol-A on Neural Stem Cells Proliferation and Differentiation in the Rat Brain Are Dependent on Wnt/ β -Catenin Pathway

摘要: Neurogenesis, a process of generation new neurons, occurs throughout the life in hippocampus and sub-ventricular zone (SVZ). Bisphenol-A (BPA), an endocrine disrupter used as surface coating for packaged food cans, injures developing adult brain. However, effects BPA on neurogenesis underlying cellular molecular mechanism(s) are still unknown. Herein, we studied effect(s) prenatal early postnatal exposure low dose Wnt/β-catenin signaling pathway that controls different steps such neural stem cell (NSC) proliferation neuronal differentiation. Pregnant rats were treated with 4, 40, 400 μg BPA/kg body weight orally daily from gestational day 6 to 21. Both vivo vitro studies showed alters NSC impaired (5′-bromo-2′-deoxyuridine (BrdU+) nestin+ cells) differentiation (BrdU/doublecortin+ BrdU/neuronal nuclei (NeuN+) SVZ compared control. It significantly altered expression/protein levels neurogenic genes Wnt hippocampus. reduced β-catenin p-GSK-3β decreased nuclear translocation, cyclin-D1 TCF/LEF promoter luciferase activity. Specific activation blockage suggested involvement this BPA-mediated inhibition neurogenesis. Further, GSK-3β activity by SB415286 small interfering RNA (siRNA) attenuated BPA-induced downregulation Overall, these results suggest significant inhibitory rat via pathway.