Lateromedial Gradient of the Susceptibility of Midbrain Dopaminergic Neurons to Neonatal 6-Hydroxydopamine Toxicity

The topography-dependent vulnerability of midbrain dopaminergic neurons to neonatal intracranial exposure to 6-hydroxydopamine (6-OHDA) was investigated at adult age by the quantitative analysis of cell counts of tyrosine hydroxylase-immunopositive neurons. In all cases of intracisternal 6-OHDA treatment, A9 dopaminergic neurons in the substantia nigra (SN) were much more vulnerable to death than more medially located A10 dopaminergic neurons. Moreover, within each cell group, there were also lateromedial topographic gradients. In the A9 neuronal group, cells located in the pars lateralis of the SN and the lateral part of the pars compacta of the SN were more susceptible to 6-OHDA toxicity than those located more medially. In the A10 neuronal group, cells located in the medial part of the ventral tegmental area were more resistant to toxicity than those located more laterally, and dopaminergic cells in the midline midbrain areas (interfascicular nucleus and rostral linear nucleus of raphe) were completely spared from 6-OHDA toxicity. These findings revealed that 6-OHDA is not equally toxic to all midbrain dopaminergic neurons in neonates and that the lateromedial vulnerability pattern shows similarities to those reported in Parkinson's disease.