Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.
Détails
Télécharger: BIB_91FD99554B4D.P001.pdf (461.80 [Ko])
Etat: Public
Version: Final published version
Etat: Public
Version: Final published version
ID Serval
serval:BIB_91FD99554B4D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.
Périodique
Plos One
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
5
Numéro
5
Pages
e10832
Langue
anglais
Résumé
While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2(Akita/+) mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2(Akita/+) and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2(Akita/+) mice and sex-matched littermate controls. Our phenotypic analysis of Ins2(Akita/+) mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM.
Mots-clé
Animals, Behavior, Animal, Diabetes Mellitus, Type 1/genetics, Diabetes Mellitus, Type 1/physiopathology, Diabetic Neuropathies/genetics, Diabetic Neuropathies/physiopathology, Ganglia, Spinal/metabolism, Ganglia, Spinal/pathology, Gene Expression Profiling, Gene Expression Regulation, Insulin/metabolism, Mice, Mice, Inbred C57BL, Motor Activity/physiology, Myelin Sheath/metabolism, Myelin Sheath/pathology, Oligonucleotide Array Sequence Analysis, Peripheral Nerves/metabolism, Peripheral Nerves/pathology, Phenotype, Schwann Cells/metabolism, Schwann Cells/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/09/2011 19:07
Dernière modification de la notice
20/08/2019 15:55