title: Peripheral inflammation increases the deleterious effect of CNS inflammation on the nigrostriatal dopaminergic system.
abstract: Evidence supports the role of inflammation in the development of neurodegenerative diseases. In this work, we are interested in inflammation as a risk factor by itself and not only as a factor contributing to neurodegeneration. We tested the influence of a mild to moderate peripheral inflammation (injection of carrageenan into the paws of rats) on the degeneration of dopaminergic neurons in an animal model based on the intranigral injection of lipopolysaccharide (LPS), a potent inflammatory agent. Overall, the treatment with carrageenan increased the effect of the intranigral injection of LPS on the loss of dopaminergic neurons in the SN along with all the other parameters studied, including: serum levels of the inflammatory markers TNF-α, IL-1β, IL-6 and C-reactive protein; activation of microglia, expression of proinflammatory cytokines, the adhesion molecule ICAM and the enzyme iNOS, loss of astrocytes and damage to the blood brain barrier (BBB). The possible implication of BBB rupture in the increased loss of dopaminergic neurons has been studied using another Parkinson's disease animal model based on the intraperitoneal injection of rotenone. In this experiment, loss of dopaminergic neurons was also strengthened by carrageenan, without affecting the BBB. In conclusion, our data show that a mild to moderate peripheral inflammation can exacerbate the degeneration of dopaminergic neurons caused by a harmful stimulus.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain.
authors.forename: Ma Carmen
authors.initials: MC
authors.lastname: Hernández-Romero
authors.forename: M José
authors.initials: MJ
authors.lastname: Delgado-Cortés
authors.forename: Manuel
authors.initials: M
authors.lastname: Sarmiento
authors.forename: Rocío M
authors.initials: RM
authors.lastname: de Pablos
authors.forename: Ana María
authors.initials: AM
authors.lastname: Espinosa-Oliva
authors.forename: Sandro
authors.initials: S
authors.lastname: Argüelles
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Bández
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Villarán
authors.forename: Raquel
authors.initials: R
authors.lastname: Mauriño
authors.forename: Marti
authors.initials: M
authors.lastname: Santiago
authors.forename: José L
authors.initials: JL
authors.lastname: Venero
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Herrera
authors.forename: Josefina
authors.initials: J
authors.lastname: Cano
authors.forename: Alberto
authors.initials: A
authors.lastname: Machado
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001479:Basal Ganglia / Q000378:metabolism* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002351:Carrageenan; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone; D020955:Striatonigral Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012402:Rotenone; D018799:Intercellular Adhesion Molecule-1; D002351:Carrageenan; D002097:C-Reactive Protein; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D004298:Dopamine