Effects of chronic expression of IL-1 in the substantia nigra

CARINA CINTIA FERRARI; MARÍA CLARA POTT GODOY; MARIELA CHERTOFF; RODOLFO TARELLI; FERNANDO PITOSSI

Amsterdam

Congreso; 7th European Meeting on Glial Cell Function in Health and Disease; 2005

Neuronal death in the substantia nigra (SN) in Parkinson´s disease (PD) is highly associated with gliai activation. The effects of pro-inflammatory cytokines in animal models of PD are controversial. No study to-date has examined the consequences of the chronic expression of pro-inflarnmatory cytokines in the SN.The aim of this study is to investigate the effects of a chronic expression of a key pro-inflarnmatory cytokine, IL-lbeta, in the SN. We characterized the effect of this cytokine on motor behavior, neurodegeneration, glial activation and the expression pattern of cytokines expression, using a recombinant adenovirus expressing IL-I (AdIL-I). Thechronic expression of IL-I induce unilateral akinesia in the contralateral paw to injection evaluated with the cylinder and the adjusting step tests at 21, 40 and 60 days postinjection. This akinesia is accompanied by a decrease ofTyroxine hydroxylase positive cells (TH+) in the SN and glial cell activation. At early time points, the inflammatory infiltrate consisted of neutrophils and macrophages but at 40 and 60 days the infíltrate switched to rnacrophages with no presence of neutrophils. IL-I exhibited a peak of expression at 7 days and decreased at 21 days, but no detectable TNF expression was found at any time point studied. the chronic expression  of a single cytokine  as IL-I in the SN induces akinesia in the contralateral paw, inflammatory infiltrate, neuronal loss and glial cell activation. These results suggest that the chronic inflammation induced by IL-I mimics both the cell loss and the motor deficits associated  with PD.