GABA,NMD A And AcH Mediate VPA Affecting The Development Of Chicken Embryo Nervous System

Objective Valproic acid(VPA)is a drug commonly used in the treatment of epilepsy and bipolar disorder.Although it is widely used,it also produces many side effects.Taking VPA during pregnancy affects fetal neurodevelopment and causes neurological diseases such as autism.In this paper,chicken embryo was used as experimental subject to study the effect of VPA on embryonic neural development and function,and further explore the molecular mechanism of VPA affecting neural development and function.Methods In this paper,chicken embryos were used as the research object.Different concentrations of VPA(3 mg/mL,4 mg/mL,5 mg/mL)were injected at E8-E14 for 7 days,and the dose was 0.1 mL per injection.The effects of VPA on the neural development of chicken embryo embryos were investigated by Nissl staining,apoptosis detection,and gene detection of BDNF,SYN,NL1 and Bcl-2 expression.The effects of VPA on neurotransmitter function were studied by detecting the expression of GABA-related genes GAD65,GAD67,GABBR2 and vGAT,and the expression of excitatory neurotransmitters NMDA receptors NR1,NR2A,NR2B and NR2C.The molecular mechanism of VPA affecting gene expression was further explored by immunohistochemistry to detect the expression of histone H3 and H4.Results(1)VPA increased chicken embryo mortality.With the increase of VPA concentration,the chicken embryo mortality increased correspondingly,and the number of chicken embryos was reduced.The chicken embryo weight had no significant effect,but the ratio of brain weight to embryo weight was significantly reduced.(2)VPA affects neuronal morphology,resulting in irregular cell arrangement,unclear cell structure,aggregation of neuronal cells,formation of pores,and gaps between cells.TUNEL detection increased the number of TUNEL-positive cells after VPA treatment,and induced neuronal apoptosis.And reduce the expression of genes involved in neural development.(3)VPA affects neurotransmitter function,increases the expression of GABA-related genes in inhibitory neurotransmitters,and decreases the expression of NMDA receptor-related genes in excitatory neurotransmitters.(4)VPA increases the expression of acetylated histones H3 and H4 in DNA.Conclusion VPA reduces the expression level of nerve development-related genes,which may affect neuronal morphology,induce apoptosis,and alter gene expression by increasing the expression level of acetylated histones in DNA,affecting neurodevelopment and function.