Adenoviral gene transfer of neurotrophic factors to injured adult motoneurons

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（CT 1）、转化生长因子-β2（TGFβ2）和胰岛素样生长因子-1（IGF 1）的重组腺病毒载体对损伤的成年大鼠面运动神经元的神经保护作用。将成年Fischer 344雄性大鼠的右侧面神经撕脱并从茎乳孔中取出，并将腺病毒载体注射到面管内。动物撕脱并用编码GDNF、BDNF、CNTF、CT 1、TGFβ2和IGF 1的腺病毒处理后，在受损的面运动神经元中分别显示出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。在撕脱伤后用编码GDNF、BDNF或TGFβ2的腺病毒治疗显著防止了损伤的面运动神经元的丢失，提高了胆碱乙酰转移酶免疫反应性，并防止了这些神经元中一氧化氮合酶活性的诱导。然而，用编码CNTF、CT 1或IGF 1的腺病毒治疗未能保护撕脱后的这些神经元。这些结果表明，腺病毒介导的GDNF、BDNF和TGFβ2基因转移，而不是CNTF、CT 1或IGF 1，可以防止成年人运动神经元损伤和运动神经元疾病的运动神经元变性。

We examined neuroprotective effects of recombinant adenoviral vectors encoding glial cell linederived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT 1), transforming growth factor-β2 (TGFβ2), and insulin-like growth factor-1 (IGF1) 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, TGFβ2 and IGF1 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 TGFβ2 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 adenovirus-mediated gene transfer of GDNF and BDNF and TGFβ2 but not CNTF, CT1 or IGF1 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.