title: Altered neurotrophin mRNA levels in peripheral nerve and skeletal muscle of experimentally diabetic rats.
abstract: The levels of neurotrophin mRNA in sensory ganglia, sciatic nerve, and skeletal muscle were measured in the streptozotocin-diabetic rat using northern blotting. Periods of diabetes of 4, 6, and 12 weeks significantly elevated brain-derived neurotrophic factor (BDNF) mRNA levels in soleus muscle compared with age-matched controls, the increase being highest at 6 weeks. At all time periods studied, the levels of nerve growth factor (NGF) mRNA in soleus muscle were decreased by 21-47%. Following 12 weeks of diabetes, BDNF mRNA levels were increased approximately two- to threefold in L4 and L5 dorsal root ganglia (DRG), and in sciatic nerve, NGF mRNA levels were raised 1.65-fold. Intensive insulin treatment of diabetic rats for the final 4 weeks of the 12-week period of diabetes reversed the up-regulation of BDNF mRNA in DRG and muscle and NGF mRNA in sciatic nerve. All diabetes-induced changes in neurotrophin mRNA were not paralleled by similar alterations in the levels of beta-actin mRNA in muscle and nerve, or of GAP-43 mRNA in DRG and nerve. It is proposed that the up-regulation of neurotrophin mRNA is an endogenous protective and/or repair mechanism induced by insult and, as such, appears as an early marker of peripheral nerve and muscle damage in experimental diabetes.
authors.affiliation: Department of Pharmacology, Queen Mary and Westfield College, University of London, England.
authors.forename: P
authors.initials: P
authors.lastname: Fernyhough
authors.forename: L T
authors.initials: LT
authors.lastname: Diemel
authors.forename: W J
authors.initials: WJ
authors.lastname: Brewster
authors.forename: D R
authors.initials: DR
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019922:GAP-43 Protein; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009132:Muscles / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D007328:Insulin; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins