Sakamoto Tsuyoshi, Kawazoe Yoko, Shen Jin-Song, Takeda Yasuo, Arakawa Yoshihiro, Ogawa Junko, Oyanagi Kiyomitsu, Ohashi Toya, Watanabe Kazutada, Inoue Kiyoharu, Eto Yoshikatsu, Watabe Kazuhiko
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
J Neurosci Res. 2003 Apr 1;72(1):54-64. doi: 10.1002/jnr.10558.
We examined neuroprotective effects of recombinant adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT1), insulin-like growth factor-1 (IGF1), and transforming growth factor-beta2 (TGFbeta2) on lesioned adult rat facial motoneurons. The right facial nerves of adult Fischer 344 male rats were avulsed and removed from the stylomastoid foramen, and adenoviral vectors were injected into the facial canal. Animals avulsed and treated with adenovirus encoding GDNF, BDNF, CNTF, CT1, IGF1 and TGFbeta2 showed intense immunolabeling for these factors in lesioned facial motoneurons, respectively, indicating adenoviral induction of the neurotrophic factors in these neurons. The treatment with adenovirus encoding GDNF, BDNF, or TGFbeta2 after avulsion significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase immunoreactivity and prevented the induction of nitric oxide synthase activity in these neurons. The treatment with adenovirus encoding CNTF, CT1 or IGF1, however, failed to protect these neurons after avulsion. These results indicate that the gene transfer of GDNF and BDNF and TGFbeta2 but not CNTF, CT1 or IGF1 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
我们研究了编码胶质细胞源性神经营养因子（GDNF）、脑源性神经营养因子（BDNF）、睫状神经营养因子（CNTF）、心肌营养素-1（CT1）、胰岛素样生长因子-1（IGF1）和转化生长因子-β2（TGFβ2）的重组腺病毒载体对成年大鼠面神经运动神经元损伤的神经保护作用。成年Fischer 344雄性大鼠的右侧面神经被撕脱并从茎乳孔取出，腺病毒载体被注入面神经管。用编码GDNF、BDNF、CNTF、CT1、IGF1和TGFβ2的腺病毒进行撕脱和治疗的动物，在损伤的面神经运动神经元中分别显示出对这些因子的强烈免疫标记，表明腺病毒诱导了这些神经元中的神经营养因子。撕脱后用编码GDNF、BDNF或TGFβ2的腺病毒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，并防止这些神经元中一氧化氮合酶活性的诱导。然而，用编码CNTF、CT1或IGF1的腺病毒治疗未能在撕脱后保护这些神经元。这些结果表明，GDNF、BDNF和TGFβ2的基因转移而非CNTF、CT1或IGF1的基因转移可能预防患有运动神经元损伤和运动神经元疾病的成年人类运动神经元的退化。
