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Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease.

Authors: Villaran, RF  Espinosa-Oliva, AM  Sarmiento, M  De Pablos, RM  Arguelles, S  Delgado-Cortes, MJ  Sobrino, V  Van Rooijen, N  Venero, JL  Herrera, AJ  Cano, J  Machado, A 
Citation: Villaran RF, etal., J Neurochem. 2010 Sep;114(6):1687-700. doi: 10.1111/j.1471-4159.2010.06879.x. Epub 2010 Aug 19.
Pubmed: (View Article at PubMed) PMID:20584104
DOI: Full-text: DOI:10.1111/j.1471-4159.2010.06879.x

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-alpha, IL-1beta, IL-6 and the acute phase protein C-reactive protein) and substantia nigra (tumor necrosis factor-alpha, IL-1beta, 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.


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RGD Object Information
RGD ID: 4145388
Created: 2010-11-02
Species: All species
Last Modified: 2010-11-02
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.