Soluble KDI domain of γ1 laminin protects adult hippocampus from excitotoxicity of kainic acid
Soluble KDI domain of γ1 laminin protects adult hippocampus from excitotoxicity of kainic acid
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γ1层粘连蛋白的可溶性KDI结构域保护成人海马免受红藻氨酸的兴奋性毒性
DOI：
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发表时间：
2004
影响因子：
4.2
通讯作者：
P. Liesi
中科院分区：
文献类型：
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作者：
M. Wikstén;A. Väänänen;R. Liebkind;P. Rauhala;P. Liesi
最近的数据表明，γ1层粘连蛋白的可溶性KDI结构域在体外促进人中枢神经元的存活和神经突生长（Liebkind et al. [2003] J Neurosci Res 73：637-643），并且似乎中和阻碍成年哺乳动物中枢神经系统（CNS）再生的神经胶质和髓磷脂衍生的信号。我们发现，损伤的成年大鼠新皮层和海马区的立体定位注射红藻氨酸（KA）的预防注射前的可溶性KDI域。在KDI结构域的存在下，新皮层和海马区均显示出广泛的神经胶质增生，但具有存活的神经元和神经胶质细胞，这些神经元和神经胶质细胞在单独注射KA后不存在并且该区域完全被破坏。这一结果表明，γ1层粘连蛋白的KDI结构域保护CNS免受兴奋性毒性损伤，并促进神经元和神经胶质细胞的存活。因此，KDI结构域可能是预防由神经退行性疾病、机械损伤或缺血诱导的CNS损伤的潜在药物。© 2004 Wiley利斯公司
Recent data indicate that the soluble KDI domain of γ1 laminin promotes survival and neurite outgrowth of human central neurons in vitro (Liebkind et al.[2003] J Neurosci Res 73:637–643), and seems to neutralize both glia‐ and myelin‐derived signals that hamper regeneration in the central nervous system (CNS) of adult mammals. We show that damage of adult rat neocortical and hippocampal areas by a stereotaxic injection of kainic acid (KA) is prevented by a preceding injection of the soluble KDI domain. In the presence of the KDI domain, both neocortical and hippocampal areas show extensive gliosis but have viable neurons and glial cells, which are absent and the areas fully destroyed after injection of KA alone. This result indicates that the KDI domain of the γ1 laminin protects the CNS against excitotoxic insults and promotes survival of both neurons and glial cells. The KDI domain may thus be a potential drug to prevent CNS damage induced by neurodegenerative disorders, mechanical injury, or ischemia. © 2004 Wiley‐Liss, Inc.