Impaired development of cerebellar cortex in rats treated postnatally with alpha-difluoromethylornithine.

Journal Article (Journal Article)

alpha-Difluoromethylornithine specifically and irreversibly inhibits the enzyme ornithine decarboxylase. Ornithine decarboxylase catalyses the initial step in the synthesis of polyamines, which are thought to play an essential role in growth and development of mammalian tissues. The current study examined the effects of alpha-difluoromethylornithine on the ontogenic development of the rat cerebellar cortex. Animals injected daily with alpha-difluoromethylornithine on postnatal days 1-21 suffered a deficit in the number of granule cells and many of the remaining granule cells became trapped in the molecular layer during migration. Purkinje cells were also scattered throughout the molecular layer and their mean diameter was 38% smaller than in controls. In general, the cerebellar cortex of alpha-difluoromethylornithine-treated rats failed to progress much beyond the stage of development reached in control rats during the first postnatal week. These effects of alpha-difluoromethylornithine were already clearly visible at 10-15 days of age. The final size of the cerebellum as a whole and of individual folia was markedly subnormal. These data indicate that polyamines play an obligatory role in cerebellar neurogenesis and histogenesis.

Full Text

Duke Authors

Cited Authors

  • Bartolome, JV; Schweitzer, L; Slotkin, TA; Nadler, JV

Published Date

  • May 1, 1985

Published In

Volume / Issue

  • 15 / 1

Start / End Page

  • 203 - 213

PubMed ID

  • 3925368

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/0306-4522(85)90132-0


  • eng

Conference Location

  • United States