Localization of nerve growth factor, neurotrophin-3, and glial cell line-derived neurotrophic factor in nestin-expressing reactive astrocytes in the caudate-putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/Bl mice

To address the hypothesis that reactive astrocytes in the basal ganglia of an animal model of Parkinson's disease serve neurotrophic roles, we studied the expression pattern of neurotrophic factors in the basal ganglia of C57/Bl mice that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce the degeneration of nigral dopamine neurons and parkinsonism. MPTP induced significant neuronal degeneration in the substantia nigra pars compacta as detected with Fluoro-Jade B staining, and this was accompanied by an increase in nestin-expressing astrocytes within the caudate-putamen. The number of nestin-positive reactive astrocytes in the caudate-putamen peaked within 3-5 days following MPTP treatment and then declined progressively toward the basal level by 21 days after treatment. Immunofluorescence and confocal microscopy confirmed coexpression of nestin or Ki-67 (cell proliferation marker) in glial fibrillary acid protein-positive astrocytes in the caudate-putamen. Double immunolabeling further revealed immunoreactivities for nerve growth factor (NGF), neurotrophin-3 (NT3), and glial cell line-derived neurotrophic factor (GDNF) in nestin-positive reactive astrocytes. Semiquantification of data obtained from mice 5 days after MPTP injection indicated that the majority of nestin-expressing cells expressed NGF (92%), NT3 (90%), or GDNF (86%). Our results present novel evidence of neurotrophic features among reactive astrocytes in the dopamine-depleted striatum. These nestin-expressing reactive astrocytes may therefore play neurotrophic roles in neural remodeling of the basal ganglia in Parkinson's disease.