Human Recombinant Nerve Growth Factor Replaces Deficient Neurotrophic Support in the Diabetic Rat |
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Authors: | Paul Fernyhough Lara T Diemel Jim Hardy Wendy J Brewster Liza Mohiuddin David R Tomlinson |
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Institution: | Department of Pharmacology, Medical Sciences, Queen Mary and Westfield College, University of London, Mile End Road, London El 4NS, UK |
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Abstract: | 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. |
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Keywords: | axonal transport calcitonin gene-related peptide diabetes diabetic neuropathy nerve growth factor substance |
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