Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 4; pp. 881 - 889
• Main Authors: FERNYHOUGH, P, GALLAGHER, A, AVERILL, S. A, PRIESTLEY, J. V, HOUNSOM, L, PATEL, J, TOMLINSON, D. R
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.1999
• Subjects: Animals; Associated diseases and complications; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cytoplasmic filaments; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic neuropathies; Diabetic Neuropathies - metabolism; Diabetic Neuropathies - pathology; Diabetic Neuropathies - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Ganglia, Spinal - metabolism; Ganglia, Spinal - pathology; JNK Mitogen-Activated Protein Kinases; Lumbosacral Region; Male; Medical sciences; Mitogen-Activated Protein Kinases; Motor Neurons - metabolism; Nerves; Neural Conduction - physiology; Neurofilament Proteins - metabolism; Neurons, Afferent - metabolism; Neurons, Afferent - physiology; Peroneal Nerve - metabolism; Phosphorylation; Physiological aspects; Rats; Rats, Inbred BB - genetics; Rats, Wistar; Sural Nerve - metabolism; Sural Nerve - pathology; United States; Endocrinopathy; Immunopathology; Animal model; Nervous system diseases; Phosphorylation; Rat; Rodentia; Autoimmune disease; Peripheral neuropathy; Vertebrata; Neurofilament; Mammalia; Etiology; Insulin dependent diabetes; Complication; Sensory neuron
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.4.881

Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy. P Fernyhough , A Gallagher , S A Averill , J V Priestley , L Hounsom , J Patel and D R Tomlinson Division of Neuroscience, School of Biological Sciences, University of Manchester, UK. paul.fernyhough@man.ac.uk Abstract Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and in this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat and the streptozocin-induced diabetic rat--have been used to determine whether such a phenomenon is involved in the etiology of the symmetrical sensory polyneuropathy commonly associated with diabetes. There was a two- to threefold (P < 0.05) elevation of neurofilament phosphorylation in lumbar dorsal root ganglia (DRG) of diabetic rats that was localized to perikarya of medium to large neurons using immunocytochemistry. Additionally, diabetes enhanced neurofilament M phosphorylation by 2.5-fold (P < 0.001) in sural nerve of BB rats. Neurofilaments are substrates of the mitogen-activated protein kinase (MAPK) family, which includes c-jun NH2-terminal kinase (JNK) or stress-activated protein kinase (SAPK1) and extracellular signal-regulated kinases (ERKs) 1 and 2. Diabetes induced a significant three- to fourfold (P < 0.05) increase in phosphorylation of a 54-kDa isoform of JNK in DRG and sural nerve, and this correlated with elevated c-Jun and neurofilament phosphorylation. In diabetes, ERK phosphorylation was also increased in the DRG, but not in sural nerve. Immunocytochemistry showed that JNK was present in sensory neuron perikarya and axons. Motoneuron perikarya and peroneal nerve of diabetic rats showed no evidence of increased neurofilament phosphorylation and failed to exhibit phosphorylation of JNK. It is hypothesized that in sensory neurons of diabetic rats, aberrant phosphorylation of neurofilament may contribute to the distal sensory axonopathy observed in diabetes.