Frim D M, Simpson J, Uhler T A, Short M P, Bossi S R, Breakefield X O, Isacson O
Neuroregeneration Laboratory, McLean Hospital, Belmont, Massachusetts 02178.
J Neurosci Res. 1993 Jul 1;35(4):452-8. doi: 10.1002/jnr.490350413.
Consistent with the notion that a defect in cellular energy metabolism is a cause of human neurodegenerative disease, systemic treatment with the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NPA) can model the striatal neurodegeneration seen in Huntington's disease. Previously, we have found that nerve growth factor (NGF), delivered biologically by the implantation of a genetically altered fibroblast cell-line, can protect locally against striatal degeneration induced by infusions of high doses of glutamate receptor agonists. We now report that implantation of NGF-secreting fibroblasts reduces the size of adjacent striatal 3-NPA lesions by an average of 64%. We conclude that biologically delivered NGF protects neurons against excitotoxicity and mitochondrial blockade--both energy-depleting processes--implying that appropriate neurotrophic support in the adult brain could protect against neurodegenerative diseases caused in part by energy depletion.
与细胞能量代谢缺陷是人类神经退行性疾病病因这一观点相一致的是，用线粒体复合物II抑制剂3-硝基丙酸（3-NPA）进行全身治疗可模拟亨廷顿病中所见的纹状体神经变性。此前，我们发现通过植入基因改造的成纤维细胞系生物递送的神经生长因子（NGF），可以局部保护免受高剂量谷氨酸受体激动剂输注诱导的纹状体变性。我们现在报告，植入分泌NGF的成纤维细胞可使相邻纹状体3-NPA损伤的大小平均减少64%。我们得出结论，生物递送的NGF可保护神经元免受兴奋毒性和线粒体阻滞——这两个都是能量消耗过程——这意味着成人大脑中适当的神经营养支持可以预防部分由能量消耗引起的神经退行性疾病。
