Ramaswamy Shilpa, McBride Jodi L, Herzog Christopher D, Brandon Eugene, Gasmi Mehdi, Bartus Raymond T, Kordower Jeffrey H
Department of Neuroscience, Rush University Medical Center, 1735 West Harrison Street, Suite 300, Chicago, IL 60612, USA.
Neurobiol Dis. 2007 May;26(2):375-84. doi: 10.1016/j.nbd.2007.01.003. Epub 2007 Jan 25.
Huntington's disease (HD) is a devastating neurodegenerative disease characterized by the selective loss of neurons in the striatum and cerebral cortex. This study tested the hypothesis that an adenoassociated viral (AAV2) vector encoding for the trophic factor neurturin (NTN) could provide neuroprotection in the rat 3-nitropropionic acid (3NP) model of HD. Rats received AAV2-NTN (CERE-120), AAV2-eGFP or Vehicle, followed 4 weeks later by the mitochondrial toxin 3NP. 3NP induced motor impairments were observed on the rotarod test, the platform test, and a clinical rating scale in all groups. However, each of these deficits was attenuated by AAV2-NTN (CERE-120). Stereological counts revealed a significant protection of NeuN-ir striatal neurons from 3NP toxicity by AAV2-NTN. These data support the concept that AAV2-NTN might be a valuable treatment for patients with Huntington's disease.
亨廷顿舞蹈症（HD）是一种毁灭性的神经退行性疾病，其特征是纹状体和大脑皮层中的神经元选择性丧失。本研究检验了以下假设：编码神经营养因子神经营养素（NTN）的腺相关病毒（AAV2）载体可在HD大鼠3-硝基丙酸（3NP）模型中提供神经保护作用。大鼠接受AAV2-NTN（CERE-120）、AAV2-eGFP或载体，4周后给予线粒体毒素3NP。在所有组的转棒试验、平台试验和临床评分量表上均观察到3NP诱导的运动障碍。然而，这些缺陷中的每一项都被AAV2-NTN（CERE-120）减轻。体视学计数显示，AAV2-NTN可显著保护NeuN免疫反应性纹状体神经元免受3NP毒性。这些数据支持以下概念：AAV2-NTN可能是亨廷顿舞蹈症患者的一种有价值的治疗方法。
