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Neurotrophins and peripheral neuropathy
D R Tomlinson1, P Fernyhough, L T Diemel
1Department of Pharmacology, Medical Sciences, Queen Mary and Westfield College, London, U.K.
Summary
Diabetic neuropathy involves deficits in nerve growth factor (NGF) and neurotrophin-3 (NT-3). Restoring these neurotrophic factors improved nerve function in diabetic rats, suggesting a key therapeutic target.
Area of Science:
- Neuroscience
- Endocrinology
- Diabetology
Background:
- Diabetic neuropathy is a common complication of diabetes mellitus.
- Rodent models show reduced nerve growth factor (NGF) and its receptor (trkA) in diabetes.
- This leads to impaired support of sensory neurons and reduced neuropeptides (substance P, CGRP).
Purpose of the Study:
- To investigate the role of neurotrophic factors in diabetic neuropathy.
- To assess the therapeutic potential of NGF and NT-3 in diabetic neuropathy models.
Main Methods:
- Examined expression of NGF, trkA, substance P, and CGRP in diabetic rat models.
- Administered intensive insulin therapy and exogenous NGF to diabetic rats.
- Assessed the effects of recombinant NT-3 on nerve conduction velocities in diabetic rats.
Main Results:
- Intensive insulin normalized NGF and neuropeptide deficits in diabetic rats.
- Exogenous NGF administration increased NGF and neuropeptide levels beyond control levels.
- NT-3 deficiency was observed in diabetic rat leg muscle; NT-3 administration improved sensory nerve conduction velocity.
Conclusions:
- Deficient neurotrophic support is implicated in the pathogenesis of diabetic neuropathy.
- Correction of neurotrophic deficits represents a critical therapeutic strategy for diabetic neuropathy.