Synaptic ultrastructural alterations anticipate the development of neuroaxonal dystrophy in sympathetic ganglia of aged and diabetic mice

Robert E. Schmidt, Curtis A. Parvin, Karen G. Green

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Neuroaxonal dystrophy, a distinctive axonopathy characterized by marked enlargement of distal axons, is the hallmark pathologic alteration in aged and diabetic human prevertebral sympathetic ganglia and in corresponding rodent models. Neuroaxonal dystrophy is thought to represent the abnormal outcome of cycles of synaptic degeneration and regeneration; a systematic study of identified axon terminals in aged and diabetic prevertebral ganglia, however, has not previously been performed. We examined the initial changes that develop in presynaptic and postsynaptic elements in sympathetic ganglia of aged and diabetic mice and found numerous synaptic changes involving both presynaptic and postsynaptic elements. Early alterations in presynaptic axon terminal size, vesicle content, and morphology culminate in the development of anastomosing membranous tubulovesicular aggregates, accumulation of autophagosomes, and amorphous debris that form a continuum with progressively larger classically dystrophic swellings. Dendritic changes consist of the development of swellings composed of delicate tubulovesicular elements and mitochondriopathy characterized by increased numbers of small mitochondria and, exclusively in aged ganglia, megamitochondria. These results support the hypothesis that neuroaxonal dystrophy results from progressive changes in presynaptic axon terminals that likely involve membrane dynamics and which are accompanied by distinctive changes in postsynaptic dendritic elements.

Original languageEnglish
Pages (from-to)1166-1186
Number of pages21
JournalJournal of neuropathology and experimental neurology
Volume67
Issue number12
DOIs
StatePublished - Dec 2008

Keywords

  • Aging
  • Autonomic neuropathy
  • Dendritic dystrophy
  • Diabetic neuropathy
  • Mitochondriopathy
  • Neuroaxonal dystrophy

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