Mediation Of Wnt/PCP-JNK Signal Pathway On NTDs Happening And Preventing NTDs With Taurine

Objective:(1) to explore the protection effect of taurine on nerve cells and itsmolecular mechanism;(2) to investigate the action mechanism of Wnt/PCP-JNKsignaling pathway in NTDs occurrence and in the mediation of taurine to preventNTDs.MethodsPart I: In vitro cultivation of immortality hippocampus neurons in mice.4groups were designed:(1) the normal control group (NC group);(2) Glutamateinjury apoptosis group (GIA group);(3) low-dose taurine protection group (LDTPgroup); and (4) high-dose taurine protection group (HDTP group). Cell growthconditions were observed under microscope. MTT assay was used to detect the cellsurvival rates, while immunofluorescence and Western Blot were adopted to detectthe expression of caspase-9.Part II: Neural tube defects model in mice induced by retinoic acid.3groupswere designed:(1) the normal control group (NC group);(2) retinoic aciddeformed group (RCD group); and (3) the taurine intervention group (TI group).Neural tube defects was counted under dissecting microscope, whileimmunofluorescence and Western Blot were adopted to detect the expression ofDvl, RhoA and JNK.ResultsPart I: A number of cells could be seen in good condition in NC group; fewer cells were in GIA group; taurine protection groups had better cell growth than theinjury group. MTT monitoring for cell viability: injured by glutamate, cellviability of hippocampal neurons was decreased obviously, and the difference wasstatistically significant compared with NC group and taurine groups;Immunofluorescence and Western blot results showed that the positive expressionof Caspase9was significantly higher in GIA group than the NC group, while thosein taurine protection groups were obviously decreased compared with the injurygroup.Part II: Under dissecting microscope, RCD group mainly showedencephalocele deformity, with higher deformity rate than the control group; TIgroup had slight encephalocele, which was significantly lower than the RCD group.Immunohistochemical detection showed DVL and RhoA were both widelyexpressed on neuroepithelial cells of the neural tubes; compared with the NCgroup, DVL and RhoA were obviously increased in the RCD group at E9.5andE10.5, while those in RCD group were reduced significantly compared with TIgroup. Western blot on DVL and RhoA showed DVL, RhoA and p-JNK weresignificantly higher at E9.5and E10.5in RCD group than the NC group, whilethose in TI group were also lower than the RCD group.Conclusions(1)Taurine can obviously decrease Caspase9activation and inhibit theapoptosis of nerve cells, thus playing a neuroprotective role.(2) Downstream RhoA was increased synchronously as the enhancedexpression of DVL-the key protein of Wnt/PCP-JNK signaling pathway. ThusJNK was activated for phosphorylation, which was involved in the occurrence ofneural tube defects.(3) Taurine had prevention effect on occurrence of neural tube defects, whose mechanism was related with the inhibition action of taurine by inhibiting theWnt/PCP-JNK signaling proteins pathways.