Dendritic development of Purkinje and granule cells in the cerebellar cortex of rats treated postnatally with alpha-difluoromethylornithine.

Postnatal administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), is known to curtail replication of granule cells in the cerebellum of the rat, but its effects on post-proliferative neurons is unknown. This Golgi study assessed the influence of daily postnatal injections of DFMO on dendritic development of the Purkinje and granule cells. Although the overall appearance of the Purkinje cells was normal, DFMO affected morphogenesis by causing: 1) a reduction in somatic growth, 2) an elongation of the primary dendrite, 3) a lengthening of the distance between the soma and the pial surface, 4) a reduction in the number of tertiary dendrites, and 5) a disruption of the distribution of the tertiary branches. Many of these effects of DFMO may be mediated via the reduction of granule cells rather than representing a direct effect on dendritogenesis. In addition to reducing the number of granule cells, the distribution and morphology of these cells in the DFMO-treated rats were severely affected. Many granule cells did not complete their migration and remained trapped in the molecular layer, and many of those trapped had greatly elongated dendrites that extended into the internal granule cell layer. These results suggest that ornithine decarboxylase is involved in the postproliferative processes of neuronal migration and differentiation.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology