Wnt1-Ngn2-En1/2在西玛津损伤小鼠生命早期多巴胺能神经元功能中的作用

doi:10.3969/j.issn.1004-616x.2024.06.004

Abstract

Abstract: OBJECTIVE： To investigate the role of the Wnt1-Ngn2-En1/2 signaling pathway in the herbicide simazine-induced damage to the dopaminergic neurons in embryonic and weaned mice. METHODS： Fifteen female and fifteen male healthy SPF Kunming mice were kept in containers in a 2∶1 ratio. During pregnancy，three groups of maternal mice were randomized∶control group (0.3% methyl cellulose solution)，low-dose group (50 μg/kg) and high-dose group (200 μg/kg). The tissues of the offspring on the day 8.5 (E8.5)，day 12.5 (E12.5)，and postnatal day 21 (PND21) of development were obtained. mRNA and protein expression of the Wnt1-Ngn2-En1/2 signaling pathway-related genes (Wnt1，Ngn2，En1，En2，Nr4a2 and Th) were detected using immunofluorescence hybridization (FISH)，real-time fluorescence quantitative PCR (qPCR) and Western blot. Through an open field experiment，effect of the treated pregnant mice on the autonomic behavior of PND21 female and male mice were identified. RESULTS： Western blot and qPCR data in E8.5 demonstrated that in comparison to the control group，low simazine-exposed groups had a decrease in the mRNA and protein expression of Wnt1 and Ngn2 (P<0.05)，and the high-dose group had a substantial decline in the expressions of Wnt1，Ngn2，En1 and En2 (P<0.05). The results of E12.5 embryo show the mRNA and protein expression of Nr4a2 and Th in the low-dose group declined as compared with the control group，(P<0.05)，and the expression of Nr4a2，Th，Wnt1，Ngn2，En1 and En2 in high-dose group decreased significantly compared with that in control group (P<0.05). The FISH data verified that Wnt1 mRNA expression was substantially reduced in the low-dose and high-dose sections of E8.5 and E12.5 as opposed to that of the control group (P<0.05). The high-dose group of PND21 offspring exhibited significantly reduced motor and self-exploration abilities in comparison to the male offspring of the control group (P<0.05)，and there was a notable down-regulation of Wnt1 and Th protein expressions (P<0.05). CONCLUSION： Simazine affected the development of dopaminergic neurons in male offspring through the Wnt1-Ngn2-En1/2 signaling pathway，and damaged the ability of independent behavior of male mice.

Key words: simazine, early life, neurotoxicity, dopaminergic neuron

CLC Number:

R994.6

LIU Jiaqi, WEN Jie, ZHANG Jiayu, LI Baixiang, LI Xueting. The role of Wnt1-Ngn2-En1/2 in the simazine-induced injury to the dopaminergic neurons in early life of mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(6): 444-451.

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The role of Wnt1-Ngn2-En1/2 in the simazine-induced injury to the dopaminergic neurons in early life of mice

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