Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease.
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.
Villarán
Ruth F
RF
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Espinosa-Oliva
Ana M
AM
Sarmiento
Manuel
M
De Pablos
Rocío M
RM
Argüelles
Sandro
S
Delgado-Cortés
María J
MJ
Sobrino
Verónica
V
Van Rooijen
Nico
N
Venero
José L
JL
Herrera
Antonio J
AJ
Cano
Josefina
J
Machado
Alberto
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004298:Dopamine / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D044967:Serum; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D004298:Dopamine