Mechanism of neural tube defects caused by ethionine in mice
Objective To prepare a neural tube defects(NTDs)model in mice with the structural analogue of methionine-ethionine,and investigate the effects of NTDs on the proliferation,apoptosis and migration of nerve cells.Methods Mouse NTDs embryo model was established.The C57BL/6J mice were injected intraperitoneally with 500 mg/kg ethionine after gestation to 7.5 d(E7.5),while the mice in control group were injected with the same dose of normal saline.Mouse embryos were taken at E11.5 and observed under stereomicroscope;The levels of S-adenosylhomocysteine(SAH)and S-adenosylmethionine(SAM)in plasma of pregnant mice were detected by ELISA;Western blot and RT-PCR were used to detect the expression of migration proteins E-cadherin and N-cadherin and the mRNA transcription in embryonic brain tissue.The expression of proliferation protein PCNA and apoptosis protein cleaved-Caspase3,and Wnt/β-catenin signaling pathway marker proteins β-catenin,TCF4 and C-myc were detected by Western blot.Results After the intervention of ethionine,the SAM content in pregnant mice decreased,the SAH content increased,and the SAM/SAH ratio decreased.Compared with the control group,the E-cadherin and cleaved-Caspase 3 were highly expressed and the apoptosis increased in NTDs group;The expression of N-cadherin and PCNA decreased,and the cell proliferation and migration decreased;The low expression of Wnt/β-catenin signaling pathway marker proteins β-catenin,TCF4 and C-myc indicated that the pathway was inhibited.Conclusion Ethionine may cause NTDs by promoting cell apoptosis via inhibiting Wnt/β-catenin signaling pathway and the proliferation and migration of nerve cells.
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