PC12 rat pheochromocytoma cells form tumors when transplanted into the
forebrains of 1-4-day-old neonatal rats; thereafter, the incidence of
tumor formation declines rapidly with increasing recipient age. The f
ate of PC12 cells transplanted into the forebrains of older neonates i
s thus not well defined. To examine the interactions of PC12 cells wit
h this older neural environment, we transplanted [H-3]thymidine-labele
d PC12 cells into the brains of 5-day-old rats. In the brains of anima
ls sacrificed 5 days after transplantation, clusters of labeled cells
were found in and around the lateral and third ventricles. By 11 days
after transplantation, single labeled cells were found to migrate into
the hippocampus and the nearby cerebral cortex. Occasional invasion o
f the ventral hypothalamus from the third ventricle was also observed.
Cells were rarely found to cross the midline or to invade the thalamu
s or the midbrain. The same pattern of labeling was found in the brain
s of animals sacrificed at 16 days after inoculation, suggesting that
migration was completed by that time. No tumors were detectable, despi
te the implantation of cells in and around the ventricles. Control inj
ections of [H-3]thymidine alone or of [H-3]thymidine-labeled astrocyte
s showed no labeling above background. These results suggest that PC12
cells migrate after inoculation into the brains of older neonatal rat
s. Additionally, this migration may be regionally constrained and dict
ated by the specific local trophic environment.