serval:BIB_91FD99554B4D
Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.
10.1371/journal.pone.0010832
000278221500018
20520806
de Preux Charles
A.S.
author
Verdier
V.
author
Zenker
J.
author
Peter
B.
author
Médard
J.J.
author
Kuntzer
T.
author
Beckmann
J.S.
author
Bergmann
S.
author
Chrast
R.
author
article
2010
Plos One
1932-6203
1932-6203
journal
5
5
e10832
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.
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
eng
60_published
true
peer-reviewed
University of Lausanne
mailto:serval_help@unil.ch
http://www.unil.ch/serval
http://serval.unil.ch/disclaimer
https://serval.unil.ch/notice/serval:BIB_91FD99554B4D