Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra
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-1β (IL-1β) could be involved in mediating neuronal demise. However, it is unknown whether the...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_09699961_v24_n1_p183_Ferrari |
| Aporte de: |
| Sumario: | 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-1β (IL-1β) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1β in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1β in the adult rat SN using a recombinant adenovirus expressing IL-1β. The chronic expression of IL-1β 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-1β in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1β 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. © 2006 Elsevier Inc. All rights reserved. |
|---|