Prominent expression of glial cell line-derived neurotrophic factor in human skeletal muscle

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 vi tro and rescues motor neurons from naturally occurring cell death, the pote ntial use of GDNF for treatment of motor neuron diseases has been a major f ocus of recent research. The expression of GDNF in humans, however, has not been fully examined. In the present study, we examined the expression of G DNF in adult human muscle by Northern blot, reverse transcriptase polymeras e chain reaction (RT-PCR), and immunohistochemical analyses to address phys iological 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. GDN F immunoreactivity was also observed within the axons and surrounding Schwa nn cells of peripheral nerves. However, RT-PCR detected expression of GDNF mRNA only in skeletal muscle, and not within the anterior horn cells of hum an spinal cord. These results suggest that GDNF is produced by skeletal mus cle and taken up at the nerve terminals for retrograde transport by axons. Thus, GDNF in human skeletal muscle may be involved in promoting motor neur on survival as a target-derived neurotrophic factor. J. Comp. Neurol. 402:3 03-312, 1998. (C) 1998 Wiley-Liss, Inc.