Non-Obese Diabetic Mice Rapidly Develop Dramatic Sympathetic Neuritic Dystrophy: A New Experimental Model of Diabetic Autonomic Neuropathy

Robert E. Schmidt, Denise A. Dorsey, Lucie N. Beaudet, Kathy E. Frederick, Curtis A. Parvin, Santiago B. Plurad, Matteo G. Levisetti

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2077-2091
Number of pages15
JournalAmerican Journal of Pathology
Volume163
Issue number5
DOIs
StatePublished - Nov 2003

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