The authors investigated the protective effects of a novel astrocyte-modulating agent,
arundic acid, in a 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (
MPTP) mouse model of
Parkinson's disease. Male mice received four intraperitoneal (i.p.)
injections of
MPTP (20 mg/kg) at 2 h intervals. The content of
dopamine and its metabolites in the striatum was reduced markedly 7 days after
MPTP treatment. The
delayed treatment with
arundic acid (30 mg/kg, i.p.) administered 3, 4, 5 and 6 days after
MPTP treatment did not affect the depletion of
dopamine and its metabolites in the striatum. Our immunohistochemical study with anti-
tyrosine hydroxylase antibody, anti-neuronal nuclei antibody,
anti-glial fibrillary acidic protein antibody, anti-
S 100beta antibody and anti-
nestin antibody showed that the
delayed treatment with
arundic acid had a protective effect against
MPTP-induced neuronal damage in the striatum and the substantia nigra of mice. Furthermore, this agent ameliorated the severe reductions in number of
isolectin reactive microglia in the striatum and the substantia nigra 7 days after
MPTP treatment. These results demonstrate that the inhibition of
S 100beta synthesis in astrocytes may be the major component of the beneficial effect of
arundic acid. Thus, our present findings provide that the therapeutic strategies targeted to astrocytic modulation with
arundic acid offers a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with
Parkinson's disease.