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.
Schmidt
Robert E
RE
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
Dorsey
Denise A
DA
Beaudet
Lucie N
LN
Frederick
Kathy E
KE
Parvin
Curtis A
CA
Plurad
Santiago B
SB
Levisetti
Matteo G
MG
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