These authors contributed equally to this report.
Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease
Version of Record online: 24 JUN 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 114, Issue 6, pages 1687–1700, September 2010
How to Cite
Villarán, R. F., Espinosa-Oliva, A. M., Sarmiento, M., De Pablos, R. M., Argüelles, S., Delgado-Cortés, M. J., Sobrino, V., Van Rooijen, N., Venero, J. L., Herrera, A. J., Cano, J. and Machado, A. (2010), Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease. Journal of Neurochemistry, 114: 1687–1700. doi: 10.1111/j.1471-4159.2010.06879.x
- Issue online: 2 SEP 2010
- Version of Record online: 24 JUN 2010
- Received June 11, 2010; accepted June 17, 2010.
- brain inflammation;
- dopaminergic neurodegeneration;
- macrophage depletion;
- Parkinson’s disease;
- ulcerative colitis
J. Neurochem. (2010) 114, 1687–1700.
Peripheral inflammation could play a role in the origin and development of certain neurodegenerative disorders. To ascertain this possibility, a model of dopaminergic neurodegeneration based on the injection of the inflammatory agent lipopolysaccharide (LPS) within the substantia nigra was assayed in rats with ulcerative colitis (UC) induced by the ingestion of dextran sulphate sodium. We found an increase in the levels of inflammatory markers from serum (tumor necrosis factor-α, IL-1β, IL-6 and the acute phase protein C-reactive protein) and substantia nigra (tumor necrosis factor-α, IL-1β, IL-6, inducible nitric oxide synthase, intercellular adhesion molecule-1, microglial and astroglial populations) of rats with UC, as well as an alteration of the blood–brain barrier permeability and the loss of dopaminergic neurons. UC reinforced the inflammatory and deleterious effects of LPS. On the contrary, clodronate encapsulated in liposomes (ClodLip), which depletes peripheral macrophages, ameliorated the effect of LPS and UC. Peripheral inflammation might represent a risk factor in the development of Parkinson’s disease.