SURVIVAL OF AND 1-METHYL-4-PHENYLPYRIDINIUM (MPP(-NEURONS IN COCULTURE OF RAT MESENCEPHALON WITH THEIR TARGET OR NONTARGET REGIONS()) NEUROTOXICITY AGAINST DOPAMINERGIC)

It is known that dopaminergic neurons in the substantia nigra of the m esencephalon mainly project to the corpus striatum and neocortex, whil e the hippocampus receives major cholinergic projection from the septu m. In the present study, the ventral mesencephalon was cocultured with target regions of its dopaminergic neurons, the striatum and neocorte x, and with non-target regions, the hippocampus, thalamus, colliculus and cerebellum, using embryonic day-17 (E17) rats. Thus, the effects o f coculture on the survival and the 1-methyl-4-phenylpyridinium (MPP()) neurotoxicity of dopaminergic neurons were investigated. The number s of viable dopaminergic neurons were enhanced in coculture not only w ith corpus striatum or neocortex, but also with hippocampus or cerebel lum. However, the survival of dopaminergic neurons cocultured with tha lamus and colliculus were almost the same as those of controls. These findings suggest that putative factor(s), possibly target-derived neur otrophic 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 f ailed to protect dopaminergic neurons from MPP(+) neurotoxicity. The r esults suggest that even though the survival of dopaminergic neurons w as supported by coculture, the action of MPP(+), an exogeneous substan ce, surpassed the supporting capacity of the coculture conditions.