Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors
Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors
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DOI：
10.1016/j.mcn.2004.07.010
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发表时间：
2004-11-01
影响因子：
3.5
通讯作者：
Rothstein, JD
中科院分区：
文献类型：
--
作者：
Lladó, J;Haenggeli, C;Rothstein, JD
神经干细胞除了具有产生神经元和/或神经胶质的能力外，似乎还固有地分泌有益于受损神经元的神经营养因子。为了测试这种潜力，我们将神经干细胞植入脊髓培养物上或附近。当神经干细胞被放置在邻近的脊髓切片，运动神经元轴突生长的神经干细胞。此外，从神经干细胞培养物的条件培养基也能够诱导类似的轴突生长，这表明这些神经干细胞分泌的可溶性因子，具有热带和/或营养特性。ELISA检测显示，神经干细胞分泌胶质细胞源性因子（GDNF）和神经生长因子（NGF）。有趣的是，预孵育的条件培养基与GDNF阻断抗体废除轴突生长。我们还表明，神经干细胞可以保护脊髓培养物免受实验诱导的兴奋性毒性损伤。NSC的神经保护潜力通过其防止运动神经元细胞死亡的能力在体内得到进一步证实。(C)2004年爱思唯尔公司All rights reserved.
Besides their capacity to give rise to neurons and/or glia, neural stem cells (NSCs) appear to inherently secrete neurotrophic factors beneficial to injured neurons. To test this potential, we have implanted NSCs onto or adjacent to spinal cord cultures. When NSCs were placed adjacent to the spinal cord sections, motor neuron axons grew toward the NSCs. Furthermore, conditioned medium from NSCs cultures was also able to induce similar axonal outgrowth, suggesting that these NSCs secrete soluble factors that have tropic and/or trophic properties. ELISA revealed that the NSCs secrete glial cell-line-derived factor (GDNF) and nerve growth factor (NGF). Interestingly, preincubation of the conditioned medium with GDNF-blocking antibodies abolished axonal outgrowth. We also showed that NSCs can protect spinal cord cultures from experimentally induced excitotoxic damage. The neuroprotective potential of NSCs was further confirmed in vivo by their ability to protect against motor neuron cell death. (C) 2004 Elsevier Inc. All rights reserved.