INVESTIGADORES
PITOSSI Fernando Juan
artículos
Título:
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the Substantia Nigra
Autor/es:
CARINA C FERRARI; CLARA POTT GODOY; RODOLFO TARELLI; MARIELA CHERTOFF; AMAICHA M DEPINO; FERNANDO PITOSSI
Revista:
NEUROBIOLOGY OF DISEASE
Referencias:
Año: 2006 p. 183 - 193
ISSN:
0969-9961
Resumen:
The functional role of the long-lasting inflammation found in the
substantia nigra (SN) of Parkinsons disease (PD) patients and animal
models is unclear. Proinflammatory cytokines such as interleukin-1â
(IL-1â) could be involved in mediating neuronal demise. However, it
is unknown whether the chronic expression of cytokines such as IL-1â
in the SN can alter neuronal vitality. The aim of this study was to
investigate the effects of the chronic expression of IL-1â in the adult
rat SN using a recombinant adenovirus expressing IL-1â. The chronic
expression of IL-1â 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-1â
in the SN elicited most of the characteristics of PD, including
progressive dopaminergic cell death, akinesia and glial activation.
Our data suggest that IL-1â per se is able to mediate inflammatorymediated
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.