These two authors contributed equally to this paper.
The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-α, IL-1β and IFN-γ
Article first published online: 25 MAR 2002
Journal of Neurochemistry
Volume 81, Issue 1, pages 150–157, April 2002
How to Cite
Castaño, A., Herrera, A. J., Cano, J. and Machado, A. (2002), The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-α, IL-1β and IFN-γ. Journal of Neurochemistry, 81: 150–157. doi: 10.1046/j.1471-4159.2002.00799.x
- Issue published online: 25 MAR 2002
- Article first published online: 25 MAR 2002
- Received August 2, 2001; revised manuscript received December 19, 2001; accepted January 2, 2002.
- basal ganglia;
- dexamethasone protection;
- dopaminergic system;
- LPS-induced neurodegeneration;
- Parkinson's disease;
- pro-inflammatory cytokines
It is becoming widely accepted that the inflammatory response is involved in neurodegenerative disease. In this context, we have developed an animal model of dopaminergic system degeneration by the intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation. To address the importance of the inflammatory response in the LPS-induced degeneration of nigral dopaminergic neurones, we carried out two different kinds of studies: (i) the possible protective effect of an anti-inflammatory compound, and (ii) the effect of the intranigral injection of inflammatory cytokines (TNF-α, IL-1β and IFN-γ) on dopaminergic neurones viability. Present results show that dexamethasone, a potent anti-inflammatory drug that interferes with many of the features characterizing pro-inflammatory glial activation, prevented the loss of catecholamine content, Tyrosine hydroxylase (TH) activity and TH immunostaining induced by LPS-injection and also the bulk activation of microglia/macrophages. Surprisingly, injection of the pro-inflammatory cytokines failed to reproduce the LPS effect. Taken together, our results suggest that inflammatory response is implicated in LPS-induced neurodegeneration. This damage may be due, at least in part, to a cascade of events independent of that described for TNF-α/IL-1β/IFN-γ.