Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.
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.
Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
Anne-Sophie
AS
de Preux Charles
Valérie
V
Verdier
Jennifer
J
Zenker
Bastian
B
Peter
Jean-Jacques
JJ
Médard
Thierry
T
Kuntzer
Jacques S
JS
Beckmann
Sven
S
Bergmann
Roman
R
Chrast
D000818:Animals; D001522:Behavior, Animal; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology
D007328:Insulin