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Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson's disease
Author(s) -
Depino Amaicha M.,
Earl Chris,
Kaczmarczyk Elke,
Ferrari Carina,
Besedovsky Hugo,
Del Rey Adriana,
Pitossi Fernando J.,
Oertel Wolfgang H.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2003.03014.x
Subject(s) - proinflammatory cytokine , microglia , substantia nigra , cytokine , tumor necrosis factor alpha , neuroprotection , neuroinflammation , immunology , biology , parkinson's disease , medicine , inflammation , neuroscience , disease
Microglial activation has been associated with the pathogenesis of Parkinson's disease (PD). Among the many components of this reaction, cytokines have been proposed as candidates to mediate neurodegenerative or neuroprotective effects. We investigated the interleukin‐1 system and tumour necrosis factor‐α mRNA and protein levels at different time intervals in the subacute intrastriatal 6‐hydroxydopamine rat model of PD, in parallel with the inflammatory response. Immunohistochemistry showed that microglial cells were activated from days 6–30 postlesion in the substantia nigra pars compacta. This microglial activation was accompanied by an atypical proinflammatory cytokine production: Interleukin‐1α and β mRNAs were found to be elevated 30 days post‐6‐hydroxydopamine injection (2‐ and 16‐fold, respectively), but no induction for interleukin‐1α or β at the protein level was detected by ELISA. As a control, a classical proinflammatory stimulus, namely endotoxin, was capable of inducing these cytokines at similar mRNA levels but also at the protein level. In addition, tumour necrosis factor‐α mRNA was hardly or not detected in the substantia nigra at any time point studied. Our data point out a tight control of key proinflammatory cytokine production in our model of PD. This work supports the notion that chronic neuronal death per se does not induce secretion of these proinflammatory cytokines but that an additional stimulus is necessary to stimulate proinflammatory cytokine production. The production of proinflammatory cytokines from “primed” microglia may in turn modulate disease progression as has been recently proposed in a model of prion disease.