title: Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice.
abstract: In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose-dependent manner (p<0.05) after prenatal alcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (p<0.01). Furthermore, we found that mossy cells were very sensitive to alcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (p<0.05) and decreased with the growing age. Compared with WT pups, the number of apoptotic mossy cells in the hippocampus of SMS2-/- pups increased (p<0.05). Western blotting showed that the expression of activated Caspase 8 and activated Caspase 3 of hippocampal tissue in WT pups and SMS2-/- pups increases after prenatal alcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis.
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China; Huaihe Hospital of Henan University, Kaifeng 475000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China.
authors.forename: Jiexin
authors.initials: J
authors.lastname: Deng
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China.
authors.forename: Zhanyou
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Fan
authors.affiliation: Huaihe Hospital of Henan University, Kaifeng 475000, China.
authors.forename: Weiya
authors.initials: W
authors.lastname: He
authors.affiliation: Institute of Neurobiology, Henan University, Kaifeng 475004, China. Electronic address: jinbodeng@126.com.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Deng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D013109:Sphingomyelins / Q000097:blood*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics* / Q000378:metabolism
chemical_list: D013109:Sphingomyelins; D000431:Ethanol; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8
keywords: Cell apoptosis; Ceramide; Mossy cell; Prenatal alcohol exposure; Sphingomyelin synthase 2 knockout mice