Human recombinant nerve growth factor replaces deficient neurotrophic support in the diabetic rat.
Manipulation of neurotrophic support is a developing strategy for new therapy aimed at neurodegenerative diseases. This study demonstrates reduced content and retrograde transport of endogenous nerve growth factor (NGF) in sciatic nerve of diabetic rats. There were also reductions in the diabetic rats in NGF protein and mRNA in skin and muscle of the hindlimb. These deficits correlated with reductions in substance P and calcitonin gene-related peptide--both products of NGF-influenced genes in primary afferents. These manifestations of deficient neurotrophic support were corrected by intensive insulin treatment and surmounted by administration of exogenous human recombinant NGF in a dose-related manner. Impaired neurotrophic support may, therefore, participate in the pathogenesis of diabetic and other peripheral neuropathies.
Fernyhough
P
P
Department of Pharmacology, Medical Sciences, Queen Mary and Westfield College, University of London, UK.
Diemel
L T
LT
Hardy
J
J
Brewster
W J
WJ
Mohiuddin
L
L
Tomlinson
D R
DR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects; D007328:Insulin / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012584:Sciatic Nerve / Q000187:drug effects*
D007328:Insulin; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins