Cellular distribution of interleukin-1alpha-immunoreactivity after MPTP intoxication in mice.

In young rodents, peripheral injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in a dopaminergic nigrostriatal denervation (during the first week after injection), followed by a spontaneous dopaminergic reinnervation. Sprouting from residual neurons has been proposed to account for this event. It has been shown that an inflammatory process takes place during striatal dopaminergic denervation but its consequences remain controversial. Some clues notably indicate that interleukin (IL)-1alpha may participate in MPTP-induced inflammation and promote recovery. We therefore studied the immunohistochemical localization of IL-1alpha expression in the striatum and ventral mesencephalon at different times (1, 3, 6, 16, and 30 days) after MPTP injection in mice. IL-1alpha-immunoreactivity (ir) was observed in striatum, substantia nigra pars compacta, and ventral tegmental area. Apart from a few localization in mesencephalic activated microglia, IL-1alpha was almost exclusively found in activated astrocytes. However, in the striatal parenchyma, another component of IL-1alpha-ir colocalized with tyrosine hydroxylase (TH)-ir, a marker for dopaminergic neurons. Moreover, some parenchymal TH-positive axons were also found to express the growth cone-associated protein (GAP)-43, a marker for axonal growth cones. In the striatum, IL-1alpha-ir was also detected in a non-astrocytic perivascular component, with a distribution similar to GAP-43-ir. IL-1alpha could thus directly or indirectly influence striatal reorganization after MPTP.