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

J Neurochem. 2010 Sep;114(6):1687-700. doi: 10.1111/j.1471-4159.2010.06879.x. Epub 2010 Aug 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Blood-Brain Barrier / metabolism
  • C-Reactive Protein / metabolism
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / pathology*
  • Cytokines / metabolism
  • Dextran Sulfate
  • Dopamine / physiology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / pathology
  • Male
  • Microglia / metabolism
  • Neurons / drug effects
  • Neurons / pathology
  • Nitric Oxide Synthase Type II / metabolism
  • Parkinson Disease / etiology*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Rats
  • Rats, Wistar
  • Risk Factors
  • Serum
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology*

Substances

  • Cytokines
  • Lipopolysaccharides
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • Dextran Sulfate
  • Nitric Oxide Synthase Type II
  • Dopamine