title: Nigral neurodegeneration triggered by striatal AdIL-1 administration can be exacerbated by systemic IL-1 expression.
abstract: Neuroinflammation has been proposed as an important component of Parkinson's Disease (PD) aetiology and/or progression. However, the inflammatory components and the mechanisms underlying their effects are only partially known. By injecting an adenovirus expressing IL-1 in the striatum, we provoked progressive neurodegeneration of dopaminergic cells in the substantia nigra, motor symptoms and microglial activation. All these effects were attenuated by an anti-inflammatory treatment. Interestingly, peripheral inflammatory stimuli exacerbated IL-1beta induced neurodegeneration and the central inflammatory reaction. These data provide evidence that central, chronic IL-1beta expression can trigger and systemic IL-1beta exacerbate nigral neurodegeneration and highlight the functional relevance of this cytokine in PD.
authors.affiliation: Laboratory of Regenerative and Protective Therapies of the Nervous System, Foundation Leloir Institute, IIBBA-CONICET, 435, Av Patricias Argentinas, (1405) Buenos Aires, Argentina.
authors.forename: María Clara
authors.initials: MC
authors.lastname: Pott Godoy
authors.forename: Carina Cintia
authors.initials: CC
authors.lastname: Ferrari
authors.forename: Fernando Juan
authors.initials: FJ
authors.lastname: Pitossi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D003342:Corpus Striatum / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000009:adverse effects; D005911:Gliosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D009434:Neural Pathways / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D003907:Dexamethasone; D004298:Dopamine