Petra Baum1, Joanna Kosacka2, Irina Estrela-Lopis3, Katrin Woidt4, Heike Serke4, Sabine Paeschke2, Maximilian Stockinger1, Nora Klöting5, Matthias Blüher2, Marco Dorn3, Joseph Classen1, Joachim Thiery6, Ingo Bechmann4, Klaus V Toyka7, Marcin Nowicki8. 1. Department of Neurology, University Hospital Leipzig, Liebigstr. 20, D-04103 Leipzig, Germany. 2. Department of Medicine, University of Leipzig, Liebigstr. 21, D-04103 Leipzig, Germany. 3. Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, D-04107 Leipzig, Germany. 4. Institute of Anatomy, University of Leipzig, Liebigstr. 13, D-04103 Leipzig, Germany. 5. Department of Medicine, University of Leipzig, Liebigstr. 21, D-04103 Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Disease, Liebigstr. 21, D-04103 Leipzig, Germany. 6. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (ILM), University of Leipzig, Liebigstr. 27, D-04103 Leipzig, Germany. 7. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany. 8. Institute of Anatomy, University of Leipzig, Liebigstr. 13, D-04103 Leipzig, Germany. Electronic address: Marcin.Nowicki@medizin.uni-leipzig.de.
Abstract
BACKGROUND: Iron is an essential but potentially toxic metal in mammals. Here we investigated a pathogenic role of exogenous iron in peripheral diabetic neuropathy (PDN) in an animal model for type 1 diabetes. METHODS: Diabetes was induced by a single injection of streptozotocin (STZ) in 4-month-old Sprague-Dawley rats. STZ-diabetic rats and non-diabetic rats were fed with high, standard, or low iron diet. After three months of feeding, animals were tested. RESULTS: STZ-rats on standard iron diet showed overt diabetes, slowed motor nerve conduction, marked degeneration of distal intraepidermal nerve fibers, mild intraneural infiltration with macrophages and T-cells in the sciatic nerve, and increased iron levels in serum and dorsal root ganglion (DRG) neurons. While motor fibers were afflicted in all STZ-groups, only a low iron-diet led also to reduced sensory conduction velocities in the sciatic nerve. In addition, only STZ-rats on a low iron diet showed damaged mitochondria in numerous DRG neurons, a more profound intraepidermal nerve fiber degeneration indicating small fiber neuropathy, and even more inflammatory cells in sciatic nerves than seen in any other experimental group. CONCLUSIONS: These results indicate that dietary iron-deficiency rather than iron overload, and mild inflammation may both promote neuropathy in STZ-induced experimental PDN.
BACKGROUND:Iron is an essential but potentially toxic metal in mammals. Here we investigated a pathogenic role of exogenous iron in peripheral diabetic neuropathy (PDN) in an animal model for type 1 diabetes. METHODS:Diabetes was induced by a single injection of streptozotocin (STZ) in 4-month-old Sprague-Dawley rats. STZ-diabeticrats and non-diabeticrats were fed with high, standard, or low iron diet. After three months of feeding, animals were tested. RESULTS:STZ-rats on standard iron diet showed overt diabetes, slowed motor nerve conduction, marked degeneration of distal intraepidermal nerve fibers, mild intraneural infiltration with macrophages and T-cells in the sciatic nerve, and increased iron levels in serum and dorsal root ganglion (DRG) neurons. While motor fibers were afflicted in all STZ-groups, only a low iron-diet led also to reduced sensory conduction velocities in the sciatic nerve. In addition, only STZ-rats on a low iron diet showed damaged mitochondria in numerous DRG neurons, a more profound intraepidermal nerve fiber degeneration indicating small fiber neuropathy, and even more inflammatory cells in sciatic nerves than seen in any other experimental group. CONCLUSIONS: These results indicate that dietary iron-deficiency rather than iron overload, and mild inflammation may both promote neuropathy in STZ-induced experimental PDN.