The Study Of Ceramide Regulatied Alcohol-induced The Nervous Cell Proliferation In The Mice

Accompany with community economy developing and society frequently communicating, alcoholic beverages having gradually become one of the common drinks. Since 1899, German physician William Sullivan found that pregnant women drinking could affect the fetus, toxicological effects of alcohol on the fetus gradually cause for concern. Scientists found that alcohol not only affects fetal growth and development, and lead to the deformity of organs, but also serious damage the development of fetal central nervous system. Alcohol can be a variety of ways on the central nervous system, causing nerve cells increased the programmed apoptosis or autophagy, resulting in temporary loss of function of neurons, Common nerve injury sites include the hippocampus and cerebellum, which damage the cerebellar will lead to ataxia, which the loss of the hippocampal nerve cell can cause loss of recent memory,cognitive disorders, and so on.Recent studies found that alcohol can affect neural cell proliferation, but the specific mechanism is still not very clear. We used sphingomyelin synthase 2 knockout (SMS2-/-) mice to establish the model of prenatal alcohol exposure, tried to further studying the neural toxicity and mechanism of alcohol by ceramide pathway, and provided a theoretical basis for investigating the relationship between alcohol exposure, ceramide, and nerve cells proliferation, and provided some new treatment strategy and methods for the treatment and prevention of neurological diseases caused nerve injury. Objective:In order to investigate the role and mechanism of ceramide regulation to alcohol-induced the neuronal proliferation and the new neurons formation.Methods:Using SMS2-/- mice to establish the model of prenatal alcohol exposure. The levels of serum sphingomyelin (SM) were detected with Enzymatic method in PO. In the meantime, the proliferation of granule cells in dentate gyrus and new born neurons were investigated before and after alcohol exposure with immunofluorescent labeling. The expression of PKC a in hippocampus was also tested with Western blot analysis.Results:1. Due to SMS2 gene deletion, the SM level of serum in SMS2-/- pups was significantly lower than Wild type (WT) pups (P<0.01). In the meantime, no matter in SMS2-/- or WT mice, prenatal alcohol exposure down-regulated the SM levels with dose-dependency (P<0.05).2. Ether in SMS2-/- or in WT pups, the number of proliferative neurons and new born neurons in dentate gyrus gradually decreased with the growing age. However, comparing with the WT pups, the number of proliferative neurons and new born neurons in dentate gyrus of SMS2-/- pups increased than WT mice after prenatal alcohol exposure with dose dependency (P<0.05).3. PKC a mainly could express in the hippocampal proper, dentate gyrus, cerebral cortex. PKC a protein express in SMS2-/- mouse hippocampus was lower than WT mice (.P<0.05). Prenatal alcohol exposure could up-regulate the PKC a protein expression in both WT and transgenic mouse with dose dependency (P<0.05).Conclusion:The reduction of SM level in SMS2-/- mice leads to the ceramide accumulation in brain tissue, and it provides us opportunity to study the ceremide induced-neural proliferation. Alcohol exposure during pregnancy can induce the compensatory neural proliferation and the production of new born neurons, suggesting the ceramide pathway is involved alcohol-induced neural proliferation. In the meantime, activation of PKC a was a key step to start the Cer-C1P pathway and up-regulated alcohol induced neural cell proliferation and the new neurons formation.