Survival of and 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity against dopaminergic neurons in coculture of rat mesencephalon with their target on non-target regions.

It is known that dopaminergic neurons in the substantia nigra of the mesencephalon mainly project to the corpus striatum and neocortex, while the hippocampus receives major cholinergic projection from the septum. In the present study, the ventral mesencephalon was cocultured with target regions of its dopaminergic neurons, the striatum and neocortex, and with non-target regions, the hippocampus, thalamus, colliculus and cerebellum, using embryonic day-17 (E17) rats. Thus, the effects of coculture on the survival and the 1-methyl-4-phenylpyridnium (MPP+) neurotoxicity of dopaminergic neurons were investigated. The numbers of viable dopaminergic neurons were enhanced in coculture not only with corpus striatum or neocortex, but also with hippocampus or cerebellum. However, the survival of dopaminergic neurons cocultured with thalamus and colliculus were almost the same as those of controls. These findings suggest that putative factor(s), possibly target-derived neurotrophic factor(s), emerging from the regions cocultured with ventral mesencephalon can influence the dopaminergic neurons resulting in the augmentation of survival. Cocultivation with all the regions studied failed to protect dopaminergic neurons from MPP+ neurotoxicity. The results suggest that even though the survival of dopaminergic neurons was supported by coculture, the action of MPP+, an exogeneous substance, surpassed the supporting capacity of the coculture conditions.