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Ultrastructural studies of the dying-back process. V. Axonal neurofilaments accumulate at sites of 2,5-hexanedione application: evidence for nerve fibre dysfunction in experimental hexacarbon neuropathy.

Abstract
This study examined the thesis that 2,5-dexanedione (2,5-HD) produces distal (dying-back) axonopathy by direct toxic action on nerve fibers. Single or repeated application of undiluted or 10% 2,5-HD to exposed rat sciatic nerves caused some fibres to develop focal axonal swellings filled with abnormally large numbers of 10 nm neurofilaments. Such changes occurred within four days of application and were especially prominent in equivalently treated nerve segments obtained from animals orally exposed to 0.5% 2,5-HD before surgery. Nerve fibers along the perimeter of tibial nerve fascicles exposed to 2,5-HD or 2,4-hexanedione (2,4-HD), a compound unable to produce systemic neuropathy, underwent non-specific breakdown and Schwann cell necrosis. Nerve fibres located in the centre of such fascicles only developed an hypertrophied paranuclear Schwann cell cytoplasm and did not proliferate intermediate filaments. Saline, hydrochloric acid and 1,6-hexanediol, a water-soluble hexacarbon also lacking systemic neurotoxic properties, produced no intra-fascicular changes when locally applied to the sciatic nerve. It is concluded (1) that 2,5-HD causes a giant axonal swellings by direct toxic action on the nerve fibre, (2) 2,5-HD does not induce a generalized disorder of cytoplasmic intermediate filaments and (3) primary Schwann cell changes produced by locally applied 2,5-HD or 2,4-HD are non-specific and unrelated to the formation of the giant axonal swellings.
AuthorsM J Politis, R G Pellegrino, P S Spencer
JournalJournal of neurocytology (J Neurocytol) Vol. 9 Issue 4 Pg. 505-16 (Aug 1980) ISSN: 0300-4864 [Print] United States
PMID7192310 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Glycols
  • Hexanones
  • Ketones
  • 2,5-hexanedione
  • 2,4-hexanedione
  • hexamethylene glycol
Topics
  • Animals
  • Axons (ultrastructure)
  • Cytoskeleton (ultrastructure)
  • Glycols (toxicity)
  • Hexanones (toxicity)
  • Ketones (toxicity)
  • Male
  • Myelin Sheath (ultrastructure)
  • Nervous System Diseases (chemically induced, pathology)
  • Organoids (ultrastructure)
  • Rats
  • Schwann Cells (ultrastructure)
  • Sciatic Nerve (ultrastructure)

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