Impaired axonal regeneration in acrylamide intoxication

John W. Griffin, Donald L. Price, Daniel B. Drachman

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Acrylamide is a neurotoxin known to impair regeneration of axons following nerve crush and to produce structurally abnormal regenerating sprouts. To investigate the mechanism of these abnormalities, protein synthesis and fast axonal transport were studied in acrylamide‐intoxicated and control rats 2 weeks after sciatic nerve crush. Using an in vitro preparation of sciatic nerve‐dorsal root ganglion, there was no difference in ganglion 3H‐leucine incorporation between the two groups. In these preparations of sensory axons, as well as in motor axons studied in vivo, a smaller proportion of rapidly transported radioactivity was carried beyond the crush in the acrylamide‐regenerating nerves compared to the control‐regenerating nerves. Correlative ultrastructural studies demonstrated that this difference reflected the impaired outgrowth of the acrylamide‐regenerating nerves, rather than an abnormality in fast transport. The acrylamide‐treated sprouts often developed swellings filled with whorls of neurofilaments; in addition, many sprouts ended in massively enlarged growth cones containing membranous organelles. EM autoradiography showed labeled, rapidly transported organelles accumulated in the neurofilamentous whorls, and therefore suggested that these organelles might be “trapped” or impeded in passage through these regions. However, there was no evidence that the growth cones received insufficient amounts of transported protein; in fact, the distended endings were densely labeled and apparently “ballooned” by transported organelles. These results suggest that acrylamide intoxication does not impair regeneration by diminishing the delivery of rapidly transported materials to the growing tip. Rather, the marked distention of the growth cones is interpreted as the morphological consequence of continued delivery of rapidly transported organelles into sprouts unable to utilize them in outgrowth.

Original languageEnglish (US)
Pages (from-to)355-370
Number of pages16
JournalJournal of Neurobiology
Issue number4
StatePublished - Jul 1977

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience


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