title: Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.
abstract: Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy.
authors.affiliation: Centre de Biotecnologia Animal i Terapia Gènica (CBATEG), Universitat Autònoma de Barcelona, Edifici H, Campus UAB, 08193 Bellaterra (Cerdanyola del Vallès), Spain. Anna.Serafin@uab.cat
authors.forename: Anna
authors.initials: A
authors.lastname: Serafín
authors.forename: Jessica
authors.initials: J
authors.lastname: Molín
authors.forename: Merce
authors.initials: M
authors.lastname: Márquez
authors.forename: Ester
authors.initials: E
authors.lastname: Blasco
authors.forename: Enric
authors.initials: E
authors.lastname: Vidal
authors.forename: Laia
authors.initials: L
authors.lastname: Foradada
authors.forename: Sonia
authors.initials: S
authors.lastname: Añor
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Rabanal
authors.forename: Dolors
authors.initials: D
authors.lastname: Fondevila
authors.forename: Fàtima
authors.initials: F
authors.lastname: Bosch
authors.forename: Martí
authors.initials: M
authors.lastname: Pumarola
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D020426:Sciatic Neuropathy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000276:immunology / Q000473:pathology; D020886:Somatosensory Disorders / Q000175:diagnosis / Q000503:physiopathology; D013311:Streptozocin / Q000494:pharmacology; D014855:Wallerian Degeneration / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
chemical_list: D013311:Streptozocin; D016899:Interferon-beta