Microglial activation with atypical pro-inflammatory cytokine expression in a rat model of Parkinson’s disease

AMAICHA M. DEPINO; CHRIS EARL; ELKE KACZMARCZYK; HUGO BESEDOVSKY; ADRIANA DEL REY; FERNANDO PITOSSI; WOLFGANG H. OERTEL

EUROPEAN JOURNAL OF NEUROSCIENCE

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2003 vol. 18 p. 2731 - 2742

0953-816X

Microglial activation has been associated with the pathogenesis of Parkinson's disease (PO). Among the many components of this reaction, cytokineshave been proposed as candidates to mediate neurodegenerative or neuroprotective effects. We investigated the interleukin-1 system and tumour necrosis factor-a mANA and protein levels at different time intervals in the subacute intrastriatal 6- hydroxydopamine rat modelof PO, in parallel with the infammatory response. lmmunohistochemistry 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 proinfammatory  cytokine production: lnterleukin-1a and f3  mANAs were found to be elevated 30 days post-6-hydroxydopamine injection (2- and 16-fold, respectively), but no induction for interleukin-1a or f3 at the protein level was detectedby EllSA. As a control,a classical proinfammatory stimulus,namely endotoxin, was capableof inducing these cytokines at similarmANA levels but also at the protein level. ln addition, tumournecrosis factor-a mANA was hardly or not detectedin the substantia nigra at any time point studied. Our data point out a tight control of key proinfammatory cytokineproduction in our model of PO. This work supports the notionthat chronic neuronaldeath per se does not induce secretion of these proinfammatory  cytokines but that an additional stimulus is necessary to stimulate proinfammatory cytokine production. The production of proinfammatory cytokines from   primed'' microglia may in turn modulate disease progression as has been recently proposed in a model of prion disease.