Study of Microglial and Astroglial Alterations Induced by Acute 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment in Mouse Brain

Abstract

The precise mechanism(s) of Parkinson’s disease, a progressive neurodegenerative disorder affecting a large number of people worldwide, is far from clearly understood. For disease induction in mouse model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is used that specifically destroys those neurons of basal ganglia and the substantia nigra that are involved in Parkinsonism. However, the effect of MPTP treatment on glial cells that play significant role in maintaining brain homeostasis remains unexplored. In view of this, the present study was designed to investigate the status of microglia and astrocytes in substantia nigra as well as in hippocampus, the region related to memory processing and cognition, in mouse brain upon MPTP administration. We examined the neuropathological alterations in hippocampus and substantia nigra upon MPTP administration by using western blot, quantitatitative PCR, immunohistochemistry and immunofluorescence. Subcutaneous administration of MPTP in Swiss mice resulted in degeneration of nigrostriatal dopaminergic neurons. In addition, there was marked microglial activation and neuroinflammation in both the substantia nigra and the hippocampus. Astrocytes also showed activation at early phase (day 1 post treatment), but it was substantially reduced in substantia nigra at day 3 post treatment. However, the number of astrocytes remained reduced in the hippocampus throughout the post-treatment period. Consistent microglial activation and neuroinflammation with gradual decline in the number of astrocytes in both substantia nigra and hippocampus appear causally associated with MPTP-induced progressive degeneration of mouse brain.