GDNF EXPRESSION IS INCREASED IN DENERVATED HUMAN SKELETAL-MUSCLE

Glial cell line derived neurotrophic factor (GDNF) is a potent trophic factor for several subpopulations of neurons including motor neurons. Two different transcripts of the GDNF gene (GDNF633 and GDNF555) have been detected in various tissues, including skeletal muscle. Denervat ion leads to an upregulation of GDNF633 in rat skeletal muscle, indica ting that GDNF is involved in the response of skeletal muscle to dener vation and possibly in reinnervation. To determine the role of GDNF in human neuromuscular disease, we investigated the expression of both t ranscripts in normal and denervated muscle and in muscle biopsies from Duchenne muscular dystrophy patients. GDNF expression levels were ana lyzed by competitive RT-PCR in 38 muscle specimens. Levels of both tra nscripts were significantly elevated in denervated muscle compared to normal and dystrophic muscle. Morphometric analysis of muscle-fiber ca libers and its correlation to GDNF expression revealed that higher lev els of GDNF were expressed in rapidly-progressive neurogenic atrophy, including four amyotrophic lateral sclerosis (ALS) cases, compared to cases of chronic atrophy. In dystrophic muscle, transcript levels were not significantly altered compared to normal controls. These data ind icate that denervation, but not dystrophy, enhances GDNF expression in human skeletal muscle. Thus, the increase of GDNF expression is part of the reaction of human skeletal muscle to denervation caused by moto r nerve lesion. GDNF might act on regenerating nerve fibers during mus cle fiber reinnervation. (C) 1998 Elsevier Science Ireland Ltd. All ri ghts reserved.