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

Michael J. Politis, Richard G. Pellegrino, Peter Spencer

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

This study examines the thesis that 2,5-hexanedione (2,5-HD) produces distal (dying-back) axonopathy by direct toxic action on nerve fibres. 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 fibres 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 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.

Original languageEnglish (US)
Pages (from-to)505-516
Number of pages12
JournalJournal of Neurocytology
Volume9
Issue number4
DOIs
StatePublished - Aug 1980
Externally publishedYes

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Intermediate Filaments
Nerve Fibers
Schwann Cells
Toxic Actions
Sciatic Nerve
Tibial Nerve
Hydrochloric Acid
2,5-hexanedione
Cytoskeleton
Cytoplasm
Necrosis
Water

ASJC Scopus subject areas

  • Neuroscience(all)
  • Histology
  • Anatomy
  • Cell Biology

Cite this

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title = "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 examines the thesis that 2,5-hexanedione (2,5-HD) produces distal (dying-back) axonopathy by direct toxic action on nerve fibres. 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 fibres 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 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.",
author = "Politis, {Michael J.} and Pellegrino, {Richard G.} and Peter Spencer",
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AU - Pellegrino, Richard G.

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N2 - This study examines the thesis that 2,5-hexanedione (2,5-HD) produces distal (dying-back) axonopathy by direct toxic action on nerve fibres. 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 fibres 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 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.

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