Celecoxib is widely used in pregnant women but its influence on fetal brain neurogenesis is largely unknown. The objective of the present study was to examine the influence of celecoxib to fetal brain development and to investigate whether curcumin could ameliorate celecoxib-induced neurotoxicity. Pregnant mice, cultured neurons and cultured neural progenitor cells were all treated with celecoxib with or without curcumin. The change in proliferation, differentiation and the activity of Wnt/β-catenin signaling pathway were then assessed. Here, we report that prenatal celecoxib exposure inhibited the activity of Wnt/β-catenin pathway and disrupted the proliferation of neuronal progenitor cells, leading to a decrease of newborn neurons in fetal frontal cortex. Treatment with curcumin significantly could attenuate the celecoxib-induced deficits in proliferation through activating the Wnt/β-Catenin pathway. Our study for the first time showed that maternal celecoxib administration caused detrimental effects to fetal brain development and provided an evidence of the therapeutic role of curcumin in celecoxib-induced neurotoxicity.
Keywords: Celecoxib; Curcumin; Cyclin D1; Fetus; Neurogenesis; Wnt.
Copyright © 2017. Published by Elsevier Inc.