Involvement of microglial cells in the pathogenesis of Parkinson's disease: A mice model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
Med Sci Monit 1998; 4(2): HY328-336
Available online: 1998-03-02
The aim of this study was to investigate the reaction of mice glial cells following the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - a neurotoxin that induces damage to the nigrostriatal system. Dopaminergic neurons, microglial cells and astrocytes were identified by anti-tyrosine hydroxylase (TH) antibodies,lectin from Griffonia simplicifolia (GSA-I-B4) and by the anti-glial fibrillary acidic protein (GFAP).Signs of dopaminergic neuron injury began following the 1st day after MPTP administration and progressed with time. A microglial reaction was observed throughout the first 14 days. The cells showed an increase in number and changes in their morphology. At the ultrastructural level we observed signs of phagocytosis as well as the features indicating the secretion of biological active substances. Astrocytosis followed the microglial reaction by a day and was seen from day two till the end of observation time (21st day). No signs of dopaminergic cell depletion nor glial activation were seen following the administration of MPTP with pargyline. Our study demonstrates that microglia and astrocytes are involved in the pathological process of the nigrostriatal system following MPTP administration. MPTP alone is not responsible for glial cell activation but its metabolite MPP+ and/or agents released by injured neurons may participate in this process.
Keywords: Astrocytes, dopaminergic neurons, nigrostriatal system, neurodegeneration, Pargyline, glia