Beck K D, Valverde J, Alexi T, Poulsen K, Moffat B, Vandlen R A, Rosenthal A, Hefti F
Department of Neuroscience, Genentech Inc., South San Francisco, California 94080.
Nature. 1995 Jan 26;373(6512):339-41. doi: 10.1038/373339a0.
Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.
胶质细胞源性神经营养因子（GDNF）可促进培养的胚胎多巴胺能神经元存活，其表达模式表明它作为黑质多巴胺能神经元的瞬时靶源性营养因子发挥作用。这些神经元参与运动活动、情绪状态和认知的控制，且在帕金森病中会不明原因地退化。为了测试GDNF对成年大脑中多巴胺能神经元是否具有营养作用，我们使用了一种大鼠模型，在该模型中通过横断内侧前脑束内的轴突来诱导这些神经元退化。我们在此报告，轴突切断导致黑质中表达酪氨酸羟化酶的神经元损失一半。通过在黑质附近反复注射GDNF，这种损失在很大程度上得到了预防。我们的研究结果表明，GDNF或相关分子可能对帕金森病的治疗有用。
