Trophic Effects of Striatal Proteins on Central Dopaminergic Neurons in Culture

Abstract

The dopaminergic neurons of the substantia nigra (mesencephalic region A9) appear to be influenced by trophic interactions with the tissue they innervate, the striatum. Large lesions in the striatum or the nigrostriatal tract lead to a decrease in tyrosine hydroxylase activity in the substantia nigra, mesencephalic region A9 (Reis et al. 1978). Large lesions in the striatum of newborn rats result in a substantial reduction in the number of dopaminergic neurons in the A9 region (Jaeger et al. 1983). In fact the only A9 dopaminergic neurons surviving after removal of the striatum on one side of the brain may be those which project to contralateral striatum. Jeager et al., point out that the loss of dopaminergic neurons is most likely due to loss of a trophic influence from the striatum rather than a consequence of damage to the dopaminergic axons, since transplanted dopaminergic neurons can survive despite even more extensive damage to their processes. Consistent with this trophic interaction hypothesis, co-culture of the mesencephalic dopaminergic neurons with cells from the striatum enhances both dopamine uptake and the number of neurons with detectable dopamine levels (Prochiantz et al. 1979, Hoffman et al. 1983) and the axonal plexus characteristic of the terminal region in the striatum (Hemmendinger et. al. 1981).