Adhesamine, a new synthetic molecule, accelerates differentiation and prolongs survival of primary cultured mouse hippocampal neurons
Adhesamine, a new synthetic molecule, accelerates differentiation and prolongs survival of primary cultured mouse hippocampal neurons
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DOI：
10.1042/bj20100071
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发表时间：
2010-04-15
影响因子：
4.1
通讯作者：
Terada, Sumio
中科院分区：
文献类型：
--
作者：
Hoshino, Mitsunobu;Tsujimoto, Tetsuhiro;Terada, Sumio
与基质的附着对于各种细胞如神经元和上皮细胞的存活和分化都是必不可少的。我们最近发现了一种小的合成分子，adhesamine，它可以促进哺乳动物细胞的粘附和生长。在本研究中，我们应用adhesamine原代培养海马神经元细胞，并比较其效果与PLL（聚-L-赖氨酸），这是广泛使用的细胞培养底物。在没有神经胶质细胞饲养层的情况下，在粘附胺涂覆的盖玻片上生长的神经元存活长达1个月，并且比在PLL涂覆的盖玻片上生长的细胞具有更大的活力。形态学分析表明，与adhesamine培养的神经元表现出更早的分化，即更早的轴突生长和树突的成熟与增强的轴突分支，比与PLL培养的神经元。突触的形成和突触后反应是明显的，早在4天的细胞培养与adhesamine。分化的加速是由细胞外基质中硫酸乙酰肝素到FAK（粘着斑激酶）和MAPK（促分裂原活化蛋白激酶）的信号通路的早期激活介导的。提高存活率和加速成熟的神经元暴露于adhesamine表明，这种完全合成的分子可能是一个有用的试剂培养神经元细胞。
Attachment to the substrate is essential for both survival and differentiation of various kinds of cells, such as neurons and epithelial cells. We recently found a small synthetic molecule, adhesamine, which boosts adhesion and growth of mammalian cells. In the present study, we applied adhesamine to primary cultured hippocampal neuronal cells and compared its effects with those of PLL (poly-L-lysine), which is widely used as a substrate for cell cultures. Neurons grown on adhesamine-coated coverslips survived for up to I month without a feeder layer of glial cells, and had greater viability than cells grown on PLL-coated coverslips. Morphological analysis revealed that neurons cultured with adhesamine exhibited earlier differentiation, i.e. earlier axonal outgrowth and dendritic maturation with enhanced neurite branching, than neurons cultured with PLL. Synaptic formation and postsynaptic responses were evident as early as 4 days in cells cultured with adhesamine. Acceleration of differentiation is mediated by earlier activation of the signalling pathways from heparan sulfate in the extracellular matrix to both FAK (focal adhesion kinase) and MAPK (mitogen-activated protein kinase). Improved survival rates and accelerated maturation of neurons exposed to adhesamine suggest that this completely synthetic molecule may be a useful reagent for culturing neuronal cells.