Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra.

CARINA CINTIA FERRARI; MARÍA CLARA POTT GODOY; RODOLFO TARELLI; MARIELA CHERTOFF; AMAICHA MARA DEPINO; FERNANDO JUAN PITOSSI

NEUROBIOLOGY OF DISEASE

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2006 vol. 24 p. 183 - 193

0969-9961

The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson´s disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1beta (IL-1b) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1b in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1b in the adult rat SN using a recombinant adenovirus expressing IL-1b. The chronic expression of IL-1b for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1b in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1b per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN.