GDNF and its receptor component Ret in injured human nerves and dorsal root ganglia.
Glial cell line-derived neurotrophic factor (GDNF) is trophic to motor and sensory neurones in animal models. GDNF mRNA is up-regulated in Schwann cells after peripheral nerve injury in rats. We have quantified and localized GDNF and its receptor component Ret, for the first time in any species, in injured human peripheral nerves and dorsal root ganglia (DRG) avulsed from the spinal cord. Significantly higher levels of GDNF were found in nerve distal to the site of the injury than in proximal or intact nerve, and in avulsed DRG than in post-mortem control DRG. GDNF immunostaining was seen in Schwann cells and in DRG neurones, especially of small and medium size, with significantly increased numbers of medium sized sensory neurones immunoreactive for GDNF after avulsion. Ret immunoreactivity was restricted to DRG neurones and axons, with no significant changes in numbers of positive DRG cells after injury. Our findings suggest that GDNF may play a role in injured human nerves and sensory ganglia, particularly in medium sized sensory neurones.
Bär
K J
KJ
Academic Department of Neurology, St Bartholomew's and the Royal London School of Medicine & Dentistry, Whitechapel, UK.
Saldanha
G J
GJ
Kennedy
A J
AJ
Facer
P
P
Birch
R
R
Carlstedt
T
T
Anand
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D029721:Drosophila Proteins; D005727:Ganglia, Spinal / Q000293:injuries*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009046:Motor Neurons / Q000737:chemistry; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009475:Neurons, Afferent / Q000737:chemistry; D059348:Peripheral Nerve Injuries; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*
D029721:Drosophila Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila