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  • Title: Role of nuclear transcription factor kappa B (NF-kappaB) for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine)-induced apoptosis in nigral neurons of mice.
    Author: Aoki E, Yano R, Yokoyama H, Kato H, Araki T.
    Journal: Exp Mol Pathol; 2009 Feb; 86(1):57-64. PubMed ID: 19027004.
    Abstract:
    The biochemical and cellular changes that occur following treatment with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine) are remarkably similar to that seen in idiopathic Parkinson's disease. In this study, we investigated the time course changes of NF-kappaB (Nuclear factor kappa B) p65 protein and apoptosis in the substantia nigra after MPTP treatment in mice. Four administrations of MPTP at 2 h intervals showed a significant and severe decrease of the number of TH (tyrosine hydroxylase) immunopositive neurons in the substantia nigra of mice from 5 h up to 21 days posttreatment. Densities of DAT (dopamine transporter) immunoreactivity were also significantly decreased in nigral neurons of mice from 1 up to 21 days after MPTP treatment. GFAP (glial fibrillary acidic protein) immunopositive cells were increased significantly in the substantia nigra from 5 h up to 21 days after MPTP treatment. In contrast, isolectin B(4) positive microglia were increased markedly in the substantia nigra only 3 and 7 days after MPTP treatment. On the other hand, a significant increase of NF-kappaB p65 immunoreactivity was observed mainly in glial cells of the substantia nigra from 5 h to 3 days after MPTP treatment. A significant increase of ssDNA (single stranded DNA) immunopositive apoptotic neurons was also observed in the substantia nigra from 5 h to 3 days after MPTP treatment. These results demonstrate that dopaminergic neuronal loss may be caused by apoptosis due to increased cytokines and apoptosis-related proteins via the activation of NF-kappaB in reactive astrocytes of the substantia nigra after MPTP treatment in mice. Thus our findings suggest that the inhibition of NF-kappaB activation in astrocytes may be useful intervention in Parkinson's disease and other neurogenerative disorders where apoptosis or inflammation plays a key role in disease pathogenesis.
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