Sakamoto T, Watabe K, Ohashi T, Kawazoe Y, Oyanagi K, Inoue K, Eto Y
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan.
Neuroreport. 2000 Jun 26;11(9):1857-60. doi: 10.1097/00001756-200006260-00011.
We examined neuroprotective effects of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat facial motoneurons. After facial nerve avulsion, animals locally injected into the facial canal with AxCALacZ (adenovirus encoding beta-galactosidase gene) or AxCAhGDNF showed expression of beta-galactosidase activity or intense immunolabeling for GDNF in lesioned facial motoneurons, respectively. The treatment with AxCAhGDNF after avulsion significantly prevented the loss of lesioned facial motoneurons, ameliorated choline acetyltransferase immunoreactivity, and suppressed the activity of nitric oxide synthase in these neurons. These results indicate that the adenovirus-mediated gene transfer of GDNF may prevent the degeneration of motoneurons in adult humans with peripheral nerve injury and motor neuron diseases.
我们研究了编码胶质细胞源性神经营养因子的腺病毒载体(AxCAhGDNF)对成年大鼠面神经损伤后运动神经元的神经保护作用。面神经撕脱术后,向面神经管局部注射AxCALacZ(编码β-半乳糖苷酶基因的腺病毒)或AxCAhGDNF的动物,损伤的面神经运动神经元分别显示出β-半乳糖苷酶活性表达或GDNF的强烈免疫标记。撕脱术后用AxCAhGDNF治疗可显著防止损伤的面神经运动神经元丢失,改善胆碱乙酰转移酶免疫反应性,并抑制这些神经元中一氧化氮合酶的活性。这些结果表明,腺病毒介导的GDNF基因转移可能预防成人周围神经损伤和运动神经元疾病中运动神经元的退化。