Prenatal Alcohol Exposure Induces The Mossy Cells Apoptosis In Hippocampus Of SMS2Knockout Mice

Apoptosis is a common vital phenomenon of eukaryocyte oganisms, which plays an important role inmany aspects, such as maintaining the normal growth and the stability of the inner circumstances of cells.However, some negative stimuli such as alcohol, will lead to superlative cells apoptosis, thus causingfunction damage.Exceeding alcohol during pregnancy will cause maldevelopment and abnormal organsin embryos, even badly damage the central nervous system.Hippocampus and cerebellum are very sensitiveto alcohol. Damage to cerebellum is likely to cause disorders in body coordination and superlativehippocampal cells apoptosis will lead to difficulty in memorizing and cognition.As we all know, alcoholcan cause cells apoptosis by many means. What’s more, the second messenger ceramide can mediate theprocess of cells apoptosis. However it isn’t clear whether ceramide is involved in cells apoptosis inducedby parental alcohol exposure by now. Therefore, we make use of the fact that the knockout of gene SMS2will cause ceramide to accumulate to establish the model of prenatal alcohol exposure, through which toobserve the effect of ceramide on the nerve cells apoptosis and analyze the relationship between ceramide,alcohol and nerve cells apoptosis, for the purpose of getting further knowledge about the mechanism ofalcohol toxicology to provide theories for prevention and treatment of nerve system degenerationdiseases.Objective: To investigate the role and mechanism of ceramide regulation on alcohol-induced theneuronal cells apoptosis in mice. Methods: Using wide type（WT） and sphingomyelin synthase2knockout(SMS₂^-/-) mice to establish the model of prenatal alcohol exposure. The levels of serum sphingomyelin （SM）were detected with Enzymatic method in P0. In the meantime, the apoptosis of mossy cells in hippocampuswere investigated after alcohol exposure with immunofluorescent labeling. The expression ofactivated-caspase8、activated-caspase3in hippocampus was tested with Western blot analysis. Results:â‘ WT and SMS₂^-/-mice, prenatal alcohol exposure down-regulated the SM levels with dose-dependency（P<0.05）. In the meantime, the SM level of serum in SMS₂^-/-pups was significantly lower than Wild-type（WT） pups （P<0.01）.â‘¡In both WT and SMS₂^-/-pups. The number of apoptosis moss cells in hippocampus were increased after prenatal alcohol exposure with dose dependency （P<0.05）,weredecreased with the growing age. However, comparing with the WT pups, the number of apoptosis neuronsin hippocampus of SMS₂^-/-pups increased than WT mice（P<0.05）.3. In the meantime,in WT and SMS₂^-/-pups, the express of activated-caspase8and activated-caspase3protein in hippocampus were increased afterprenatal alcohol exposure with dose dependency （P<0.05）,were decreased with the growing age. However,comparing with the WT pups, the express of activated-caspase8and activated-caspase3protein inhippocampus of SMS₂^-/-pups increased than WT mice（P<0.05）. Conclusions: The reduction of SM level inSMS₂^-/-mice leads to the ceramide accumulation in brain tissue; Ceramide as a second messenger involvedin prenatal alcohol exposed neuronal apoptosis in the process, and can promote apoptosis; Alcoholexposure during pregnancy, mainly through the death receptor pathway induces neuronal apoptosis.