Selective decrease in axonal nerve growth factor and insulin-like growth factor I immunoreactivity in axonopathies of unknown etiology.
In an attempt to approach the mechanisms underlying axonopathies of unknown etiology, we have studied by immunocytochemistry the fate of several growth factors in eight of such cases that we had previously analyzed by morphometry and which were characterized by a decrease in neurofilaments and an increase in beta tubulin immunostaining. Here we establish that, contrary to beta tubulin, growth-associated protein43 (GAP-43) immunolabeling is not up-regulated in theses cases, correlating well with the failure of regeneration. Neurotrophin-3 (NT-3) and its receptor TrkC were not modified compared to controls (five cases). On the contrary, we observed in all cases a pronounced decrease in the number of fibers labeled for nerve growth factor (NGF) and insulin-like growth factor I (IGF-I), which were both approximately half of control values. This decrease could not be ascribed to the reduction in fiber density since it was also present in cases without fiber loss (isolated large fiber atrophy). The fact that only around 50% of fibers were stained, versus all fibers in controls, probably accounted for this decrease. It contrasted also with the normality of NGF and IGF-I immunolabeling in six cases of chronic inflammatory demyelinating neuropathy that were investigated in parallel. These results differ from those reported in experimental diabetic neuropathy, during which NT-3 is also decreased. A deficient supply of specific growth factors delivered by neuronal targets may be responsible for these neuropathies and their associated axonal cytoskeleton abnormalities.
Fressinaud
Catherine
C
Department of Neurology, UPRES EA 3143, University Hospital, 4 rue Larrey, 49033 Angers, France. Catherine.fressinaud@med.univ-angers.fr
Jean
Isabelle
I
Dubas
Frédéric
F
D000328:Adult; D000368:Aged; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009138:Musculocutaneous Nerve / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology
D007334:Insulin-Like Growth Factor I; D020932:Nerve Growth Factor