Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats.
Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats.
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DOI：
10.1016/j.bbrc.2007.01.107
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发表时间：
2007-03
影响因子：
3.1
通讯作者：
Jinbo Yin;Yuxin Ma;Qing Yin;Haiwei Xu;Ning An;Shiyong Liu;Xiaotang Fan;Hui Yang
中科院分区：
文献类型：
--
作者：
Jinbo Yin;Yuxin Ma;Qing Yin;Haiwei Xu;Ning An;Shiyong Liu;Xiaotang Fan;Hui Yang
海马齿状回(DG)是成年哺乳动物大脑中为数不多的以持续神经发生为特征的区域之一。戊四氮(PTZ)点燃癫痫模型中DG颗粒细胞层神经前体细胞的增殖已被证实，但其分子机制尚不清楚。我们先前报道，骨形态发生蛋白-4(BMP4)在海马区的表达模式受发育调节，主要定位于成人的DG。为了探讨BMP4在癫痫发作中的作用，我们检测了PTZ点燃过程中DG中BMP4的表达，并结合溴脱氧尿嘧啶核苷(BrdU)标记技术探讨其与细胞增殖的关系。我们发现，BMP4水平和BrdU标记细胞的动态变化依赖于PTZ诱发癫痫易感状态的点燃阶段。PTZ点燃后1d BMP4mRNA阳性细胞数和BrdU标记细胞数达高峰，2个月后降至基础水平。此外，BMP4基因表达的增加与BrdU标记细胞数量的增加有显著相关性。用反义寡核苷酸(ASODN)有效阻断BMP4的表达后，首次注射PTZ后16d和点燃后1、3、7、14d，齿状回颗粒下带(DG-SGZ)和门区BrdU标记细胞明显减少。这些结果提示，PTZ点燃癫痫所致的海马齿状回细胞增殖增加可能受BMP4过度表达的调节。
The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process and explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after the first PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression.