Acrylamide-induced distal axon degeneration: A proposed mechanism of action

Richard M. LoPachin, E. J. Lehning

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Exposure to acrylamide (ACR) monomer produces distal swelling and subsequent degeneration in central and peripheral myelinated axons of humans and laboratory animals. The molecular and cellular events leading to this type of axonopathy are currently unknown. Herein we describe a new mechanism of ACR axonopathy that represents a synthesis of recent research findings and prior hypotheses. According to this model, ion regulation in distal paranodal axon regions is compromised by diminished axolemmal Na/K-ATPase activity. It is suggested that decreased NA/K-ATPase activity is a consequence of aberrant cell body processing and/or deficient axonal transport. Reduced Na pump activity promotes membrane depolarization in conjunction with axoplasmic accumulation of Na and loss of K. Thermodynamically, this favors reverse operation of the Na/Ca-exchanger which permits axonal Ca entry in exchange for Na. The influx of Ca eventually overwhelms buffering mechanisms and leads to distal axon degeneration. Distal axons are predisposed to regulatory failure of this type due to a dependency on cell body output and the unique differential distribution of enzymes, ion channels and exchangers among nodal and internodal regions. This heuristic model might account for axon degeneration occurring as a result of exposure to other chemical neurotoxicants and following axotomy and other forms of mechanical injury.

Original languageEnglish (US)
Pages (from-to)247-260
Number of pages14
JournalNeuroToxicology
Volume15
Issue number2
StatePublished - 1994
Externally publishedYes

Fingerprint

Acrylamide
Axons
Adenosine Triphosphatases
Cells
Axotomy
Axonal Transport
Depolarization
Laboratory Animals
Ion Channels
Swelling
Animals
Monomers
Pumps
Ions
Membranes
Wounds and Injuries
Enzymes
Processing
Research
Cell Body

Keywords

  • Acrylamide
  • Axon degeneration
  • Distal Axonopathy
  • Na/Ca-exchanger
  • Na/K-ATPase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Toxicology

Cite this

Acrylamide-induced distal axon degeneration : A proposed mechanism of action. / LoPachin, Richard M.; Lehning, E. J.

In: NeuroToxicology, Vol. 15, No. 2, 1994, p. 247-260.

Research output: Contribution to journalArticle

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