Effect of Wnt1 and Wnt5a on the development of dopaminergic neurons, and toxicity induced by combined exposure to paraquat and maneb during gestation and lactation

摘要

Paraquat (PQ) and maneb (MB) are widely used herbicides. Wingless (Wnt) proteins serve a role in the development and differentiation of dopaminergic neurons. Previous studies demonstrated that combined exposure to PQ and MB damages dopaminergic neurons in the midbrain. Effects of PQ and MB exposure on midbrain Wnt proteins have also been previously reported. In the present study, from the 5th day of gestation to weaning of the offspring, pregnant Sprague-Dawley rats were administrated saline, or PQ and MB at two different doses: high, 15 mg/kg body weight PQ + 45 mg/kg body weight MB; or low, 10 mg/kg body weight PQ + 30 mg/kg body weight MB. Dopamine content in the striatum was examined by high performance liquid chromatography with a fluorescence detector and mRNA and protein expression of Wnt1, Wnt5a, nuclear receptor related factor 1 (Nurr1) and tyrosine hydroxylase (TH) in the midbrain was examined by reverse transcription-quantitative polymerase chain reaction and western blotting. Combined exposure to PQ and MB during development decreased mRNA and protein expression of Wnt1, TH and Nurr1 and increased expression of Wnt5a in the offspring.