Protection of sensory function in diabetic rats by Neotrofin.
We investigated the ability of Neotrofin, an agent that enhances endogenous nerve growth factor (NGF) levels, to prevent phenotypic, functional and structural changes that occur in the peripheral nerve of streptozotocin-diabetic rats. Eight weeks of Neotrofin treatment prevented depletion of NGF protein in plantar foot skin and sciatic nerve of diabetic rats and increased NGF protein in associated skeletal muscles. These effects were accompanied by maintenance of normal nerve levels of the neuropeptides substance P and calcitonin gene related peptide. Thermal hypoalgesia and conduction slowing of large sensory fibres in diabetic rats were ameliorated by Neotrofin treatment, whereas there was no effect on conduction slowing in large motor fibres or on reduced myelinated fibre axonal calibre. Enhancing endogenous production of neurotrophic factors using small molecules may be an alternative to either exogenous treatment with neurotrophic factors or gene therapy as a therapeutic approach to treating diabetic neuropathy.
Calcutt
Nigel A
NA
Department of Pathology, University of California San Diego, La Jolla 92093-0612, USA. ncalcutt@ucsd.edu
Freshwater
Jason D
JD
Hauptmann
Nils
N
Taylor
Eve M
EM
Mizisin
Andrew P
AP
D062365:Aminobenzoates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007042:Hypoxanthines / Q000494:pharmacology* / Q000627:therapeutic use; D020932:Nerve Growth Factor / Q000378:metabolism; D009431:Neural Conduction; D009475:Neurons, Afferent / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism; D013311:Streptozocin; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
D062365:Aminobenzoates; D007042:Hypoxanthines; D018696:Neuroprotective Agents; C086241:4-((3-(1,6-dihyro-6-oxo-9H-purin-9-yl)-1-oxopropyl)amino)benzoic acid; D013373:Substance P; D013311:Streptozocin; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide