Suzuki H, Hase A, Miyata Y, Arahata K, Akazawa C
Department of Pharmacology, Nippon Medical School, Tokyo, Japan.
J Comp Neurol. 1998 Dec 21;402(3):303-12.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neurotrophic effects on motor neurons as well as mesencephalic dopaminergic neurons. Because GDNF promotes survival of motor neurons in vivo and in vitro and rescues motor neurons from naturally occurring cell death, the potential use of GDNF for treatment of motor neuron diseases has been a major focus of recent research. The expression of GDNF in humans, however, has not been fully examined. In the present study, we examined the expression of GDNF in adult human muscle by Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and immunohistochemical analyses to address physiological roles of GDNF in humans. Northern blot analysis demonstrated high expression of GDNF mRNA in human skeletal muscle when compared to that of mouse. Intense GDNF immunoreactivity was observed in the vicinity of plasma membranes of skeletal muscle, particularly at neuromuscular junctions. GDNF immunoreactivity was also observed within the axons and surrounding Schwann cells of peripheral nerves. However, RT-PCR detected expression of GDNF mRNA only in skeletal muscle, and not within the anterior horn cells of human spinal cord. These results suggest that GDNF is produced by skeletal muscle and taken up at the nerve terminals for retrograde transport by axons. Thus, GDNF in human skeletal muscle may be involved in promoting motor neuron survival as a target-derived neurotrophic factor.
胶质细胞系源性神经营养因子（GDNF）已被证明对运动神经元以及中脑多巴胺能神经元具有神经营养作用。由于GDNF在体内和体外均可促进运动神经元的存活，并能使运动神经元从自然发生的细胞死亡中获救，因此GDNF在运动神经元疾病治疗中的潜在应用一直是近期研究的主要焦点。然而，GDNF在人类中的表达尚未得到充分研究。在本研究中，我们通过Northern印迹法、逆转录聚合酶链反应（RT-PCR）和免疫组织化学分析，检测了GDNF在成年人类肌肉中的表达，以探讨GDNF在人类中的生理作用。与小鼠相比，Northern印迹分析显示GDNF mRNA在人类骨骼肌中高表达。在骨骼肌细胞膜附近，特别是在神经肌肉接头处，观察到强烈的GDNF免疫反应性。在外周神经的轴突和周围的施万细胞内也观察到GDNF免疫反应性。然而，RT-PCR仅在骨骼肌中检测到GDNF mRNA的表达，而在人类脊髓前角细胞中未检测到。这些结果表明，GDNF由骨骼肌产生，并在神经末梢被摄取，通过轴突进行逆行运输。因此，人类骨骼肌中的GDNF可能作为一种靶源性神经营养因子参与促进运动神经元的存活。
