Positive control of target cerebellar cells on norepinephrine uptake in embryonic brainstem cultures in serum-free medium.
Brainstem cells from 15-day-old mouse embryos (E 15) grown for 8-10 days in dissociated primary cell culture in serum-free medium show high affinity uptake for [3H]norepinephrine (NE) that is specifically inhibited by desmethylimipramine (DMI), and also show high affinity binding for [3H]DMI. Brainstem cell uptake capacity for NE is increased at least 2-fold when cocultured with target cerebellar or striatal cells of the same embryonic age. The stimulation exerted by the cerebellum appears to be developmentally regulated since more mature cerebella (from 16-17-day-old embryos) exerted a greater stimulation than younger structures (from 14-15-day-old embryos). This stimulatory effect is also correlated with the number of available target sites since increasing the amount of cerebellar cells result in an increased stimulation of uptake capacity. The high affinity binding for [3H]DMI is also enhanced in coculture. The number of noradrenergic neurons, detected by autoradiography, remains unchanged in coculture indicating that added cerebellar cells did not take up NE, suggesting that the number of uptake sites per noradrenergic neuron is increased in the presence of target cells. These results indicate that interactions between afferent and target neurons, which normally take place during in vivo development, also occur in vitro and may result in a modification of neurotransmitter uptake in the afferent neuron.
D000818:Animals; D001933:Brain Stem / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002531:Cerebellum / Q000196:embryology*; D004298:Dopamine / Q000378:metabolism; D004627:Embryonic Induction; D051379:Mice; D009434:Neural Pathways / Q000196:embryology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*
D004298:Dopamine; D009638:Norepinephrine