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[Alcohol-induced proliferation of neurons in mouse hippocampal dentate gyrus: a possible role of ceramide.] [Article in Chinese]

DENG Tong-Xing, WANG Zhi-Xin, GAO Xiao-Qun, SHI Yuan-Yuan, MA Zhan-You, JIN Hai-Xiao, DENG Jin-Bo^*

Institute of Neurobiology of Henan University, Kaifeng 475004, China； Department of Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou 450052, China； Department of Anatomy of Luohe Medical College, Luohe 462002, China

Abstract

To investigate the role and mechanism of ceramide (Cer) regulation in alcohol-induced neuronal proliferation and the newborn neurons formation, we used sphingomyelin synthase 2 (predominant enzyme of Cer metabolism) knockout (SMS2−/−) and wild type (WT) female mice to establish the model of prenatal alcohol exposure. In 24 h after being given birth (postnatal day 0, P0), the offspring of model mice received blood sphingomyelin (SM) measurement with enzymatic method. On P0, P7, P14 and P30, the proliferation of granule cells in the dentate gyrus and newborn neurons were investigated with immunofluorescent labeling. The expression of protein kinase Cα (PKCα) in the hippocampus was tested with Western blot analysis. The results showed that the SM level of blood in SMS2−/− pups was significantly lower than that in WT pups. No matter in SMS2−/− or WT mice, the prenatal alcohol exposure down-regulated the SM levels in pups with dose-dependency. In both SMS2−/− and WT pups, the number of proliferative neurons and newborn neurons in the dentate gyrus gradually decreased with the growing age. Compared with the WT pups, SMS2−/− pups showed significantly more proliferative neurons and newborn neurons in the dentate gyrus. Notably, prenatal alcohol exposure dose-dependently increased proliferative neurons and newborn neurons in the dentate gyrus in both WT and SMS2−/− pups. The hippocampal expression of PKCα protein in SMS2−/− mice was lower than that in WT mice, and prenatal alcohol exposure could up-regulate the PKCα protein expression in both WT and SMS2−/− mice with dose dependency. These results suggest that alcohol exposure during pregnancy can induce the compensatory neural cell proliferation and the production of newborn neurons in offspring, and the Cer-ceramide-1-phosphate (C1P) pathway is involved in alcohol-induced neural cell proliferation. The activation of PKCα may be a key step to start the Cer-C1P pathway and up-regulate the alcohol-induced neural cell proliferation and the newborn neurons formation.

Key words: Ceramide; neural cell proliferation; sphingomyelin synthase 2; ceramide-1-phosphate

Received: 2011-03-04　　Accepted: 2011-07-18

Corresponding author: 邓锦波　　E-mail: jinbo_deng@henu.edu.cn

Citing This Article：

DENG Tong-Xing, WANG Zhi-Xin, GAO Xiao-Qun, SHI Yuan-Yuan, MA Zhan-You, JIN Hai-Xiao, DENG Jin-Bo. [Alcohol-induced proliferation of neurons in mouse hippocampal dentate gyrus: a possible role of ceramide.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (6): 479-490 (in Chinese with English abstract).