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Involvement of dopaminergic neuronal cystatin C in neuronal injury-induced microglial activation and neurotoxicity.
- Source :
-
Journal of Neurochemistry . Aug2012, Vol. 122 Issue 4, p752-763. 12p. - Publication Year :
- 2012
-
Abstract
- J. Neurochem. (2012) 122, 752-763. Abstract Factors released from injured dopaminergic (DA) neurons may trigger microglial activation and set in motion a vicious cycle of neuronal injury and inflammation that fuels progressive DA neurodegeneration in Parkinson's disease. In this study, using proteomic and immunoblotting analysis, we detected elevated levels of cystatin C in conditioned media (CM) from 1-methyl-4-phenylpyridinium and dieldrin-injured rat DA neuronal cells. Immunodepletion of cystatin C significantly reduced the ability of DA neuronal CM to induce activation of rat microglial cells as determined by up-regulation of inducible nitric oxide synthase, production of free radicals and release of proinflammatory cytokines as well as activated microglia-mediated DA neurotoxicity. Treatment of the cystatin C-containing CM with enzymes that remove O- and sialic acid-, but not N-linked carbohydrate moieties markedly reduced the ability of the DA neuronal CM to activate microglia. Taken together, these results suggest that DA neuronal cystatin C plays a role in the neuronal injury-induced microglial activation and neurotoxicity. These findings from the rat DA neuron-microglia in vitro model may help guide continued investigation to define the precise role of cystatin C in the complex interplay among neurons and glia in the pathogenesis of Parkinson's disease. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 122
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 77825141
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2012.07826.x