Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra
Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra
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DOI：
10.1016/j.nbd.2006.06.013
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发表时间：
2006-10-01
影响因子：
6.1
通讯作者：
Juan Pitossi, Fernando
中科院分区：
文献类型：
--
作者：
Cintia Ferrari, Carina;Pott Godoy, Maria Clara;Juan Pitossi, Fernando
在帕金森病（PD）患者和动物模型的黑质（SN）中发现的长期炎症的功能作用尚不清楚。促炎细胞因子如白细胞介素-1 β（IL-1 β）可能参与介导神经元死亡。然而，尚不清楚SN中细胞因子如IL-1 β的慢性表达是否可以改变神经元活力。本研究的目的是研究使用表达IL-1 β的重组腺病毒在成年大鼠SN中慢性表达IL-1 β的效果。持续60天的IL-1 β慢性表达诱导SN中的多巴胺能细胞死亡和仅在注射后21天开始的单侧运动不能。小胶质细胞活化和炎性细胞浸润与多巴胺能细胞死亡和运动障碍有关。星形胶质细胞活化延迟，并与烧灼形成相关。单个促炎细胞因子如IL-1 β在SN中的慢性表达引起PD的大部分特征，包括进行性多巴胺能细胞死亡、运动不能和神经胶质活化。我们的数据表明，IL-1 β本身能够介导炎症介导的毒性作用，在SN中，如果它的表达是持续的。该模型将有助于确定与SN中炎症源性神经变性相关的可能治疗靶点。(c)2006年爱思唯尔公司All rights reserved.
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-1 beta (IL-1 beta) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1 beta in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1 beta in the adult rat SN using a recombinant adenovirus expressing IL-1 beta. The chronic expression of IL-1 beta 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 sear formation. The chronic expression of a single proinflammatory cytokine as IL-1 beta in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1 beta 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. (c) 2006 Elsevier Inc. All rights reserved.