Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.
To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.
Departments of Pathology and Immunology, Division of Metabolism, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. reschmidt@pathology.wustl.edu
Robert E
RE
Schmidt
Denise A
DA
Dorsey
Lucie N
LN
Beaudet
Kathy E
KE
Frederick
Curtis A
CA
Parvin
Santiago B
SB
Plurad
Matteo G
MG
Levisetti
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D003929:Diabetic Neuropathies / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005728:Ganglia, Sympathetic / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008854:Microscopy, Electron; D016511:Severe Combined Immunodeficiency / Q000473:pathology