Nigral neurodegeneration triggered by striatal AdIL-1 administration can be exacerbated by systemic IL-1 expression.
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.
Pott Godoy
María Clara
MC
Laboratory of Regenerative and Protective Therapies of the Nervous System, Foundation Leloir Institute, IIBBA-CONICET, 435, Av Patricias Argentinas, (1405) Buenos Aires, Argentina.
Ferrari
Carina Cintia
CC
Pitossi
Fernando Juan
FJ
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
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D003907:Dexamethasone; D004298:Dopamine