In vitro acrylamide exposure alters growth cone morphology

Christopher H. Martenson, Michael Sheetz, Doyle G. Graham

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Acrylamide intoxication leads to degeneration of the longest axons of the central and peripheral nervous systems in humans and laboratory animals. Axonal derangements resulting from in vivo acrylamide exposure are first noted within synapses of the longest axons before involving more proximally located axonal segments or shorter axons, thus illustrating the specificity of acrylamide for the terminal axonal regions. As a possible model system for investigating the mechanism of toxicity of acrylamide on the distal axon, we exposed neurite-extending chick dorsal root ganglion (DRG) cells to acrylamide in vitro and then examined growth cones for alterations in morphology and function. Exposing DRG explants to media containing from 0.125 to 1.0 mM acrylamide for 16 hr leads to specific and dose-responsive alterations of growth cone morphology including: a nearly total loss of filopodial elements, the preservation of highly active but two-dimensional lamellar structures, an inappropriate extension of the axonal cytoskeleton into the forward region of most growth cones, and a frequent breakdown of the central and peripheral growth cone domains. The sulfhydryl alkylating agents ethacrynic acid, iodoacetamide, and iodoacetic acid were tested and none produced acrylamide-like morphological alterations at any dose. DRG cultures were also exposed to the neurotoxic acrylamide analogs glycidamide, N-hydroxymethacrylamide (HM-ACR), and methacrylamide (M-ACR). At concentrations of 0.25 to 1.0 mM, glycidamide exposure resulted in acrylamide-like growth cone alterations. HM-ACR exposure also resulted in growth cones that were acrylamide-like but only at concentrations > 1.5 mM. M-ACR did not produce acrylamide-like cones at doses of up to 16.6 mM. Thus, in vitro exposure of DRG explants to acrylamide and two neurotoxic acrylamide analogs leads to reproducible and specific morphological alterations that are dose-dependent and separable from the effects of sulfhydryl alkylation.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalToxicology and Applied Pharmacology
Volume131
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Growth Cones
Acrylamide
Cones
Spinal Ganglia
Axons
In Vitro Techniques
Iodoacetic Acid
Ethacrynic Acid
Iodoacetamide
Lamellar structures
Alkylating Agents
Alkylation
Peripheral Nervous System
Laboratory Animals
Neurology
Neurites
Cytoskeleton
Synapses
Toxicity
Animals

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

In vitro acrylamide exposure alters growth cone morphology. / Martenson, Christopher H.; Sheetz, Michael; Graham, Doyle G.

In: Toxicology and Applied Pharmacology, Vol. 131, No. 1, 01.01.1995, p. 119-129.

Research output: Contribution to journalArticle

Martenson, Christopher H. ; Sheetz, Michael ; Graham, Doyle G. / In vitro acrylamide exposure alters growth cone morphology. In: Toxicology and Applied Pharmacology. 1995 ; Vol. 131, No. 1. pp. 119-129.
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