Expression of S-100 protein is related to neuronal damage in MPTP-treated mice.

S-100beta is a calcium-binding protein expressed at high levels in brain and is known as a marker of brain damage. However, little is known about the role of S-100beta protein during neuronal damage caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To determine whether S-100beta protein is induced in glial cells after MPTP treatment, we investigated the expression of S-100 protein immunohistochemically, using MPTP-treated mice. We also examined the change of neurons and glial cells in mice after MPTP treatment. The present study shows that tyrosine hydroxylase (TH) immunoreactivity decreased gradually in the striatum and substantia nigra from 1 day after MPTP treatment. Thereafter, TH-immunopositive cells and fibers decreased in the striatum and substantia nigra at 3 days after MPTP treatment. In contrast, S-100-immunopositive cells and glial fibrillary acidic protein (GFAP)-immunopositive cells increased markedly in the striatum and substantia nigra at 3 days after MPTP treatment. Seven days after MPTP treatment, S-100-immunopositive cells decreased in the striatum and substantia nigra. However, the number of GFAP-immunopositive cells increased in these regions. In double-labeled immunostaining with anti-S-100 and anti-GFAP antibodies, S-100 immunoreactivity was observed only in the GFAP-positive astrocytes. These results provide evidence that astrocytic activation may play a role in the pathogenesis of MPTP-induced degeneration of dopaminergic neurons. Furthermore, the present study demonstrates that S-100 protein is expressed selectively by astrocytes, but not by microglia, after MPTP treatment. These results provide valuable information for the pathogenesis of the acute stage of Parkinson's disease.