Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta.
Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta.
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DOI：
10.1016/j.neuroscience.2008.07.016
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发表时间：
2008-09-22
期刊：
影响因子：
3.3
通讯作者：
Bishops, C.
中科院分区：
文献类型：
--
作者：
Barnum, C. J.;Eskow, K. L.;Dupre, K.;Blandino, P., Jr.;Deak, T.;Bishops, C.
虽然帕金森病（PD）的病因仍然未知，但有压倒性的证据表明，神经炎症在多巴胺（DA）神经元的进行性丧失中起着关键作用。因为几乎所有患有PD的人都接受l-DOPA，所以令人惊讶的是，炎症尚未被检查为作为慢性l-DOPA治疗的结果而发生的异常不自主运动（AIM）的潜在贡献者。作为这一假设的初步检验，我们研究了外源性皮质酮（CORT），内源性抗炎剂，对左旋多巴诱导的运动障碍（LID）的表达和发展的影响，在单侧DA耗尽大鼠。为此，雄性Sprague-Dawley大鼠接受单侧内侧前脑束6-羟基多巴胺损伤。三周后，l-DOPA致敏的大鼠在l-DOPA之前接受CORT（0- 3.75mg/kg）的急性注射以评估LID的表达。第二组大鼠用于检查用CORT和l-DOPA共处理2周的l-DOPA未处理大鼠中LID的发展。记录AIM和旋转。外源性CORT剂量依赖性地减弱了AIM的表达和发育，而不影响旋转。纹状体组织的实时RT-PCR表明IL-1β在这些效应中的作用，因为在用l-DOPA处理的大鼠（在DA耗尽的纹状体内）中，其表达在损伤侧增加，并且用CORT减弱。在最后的实验中，将IL-1受体拮抗剂（IL-1 ra）显微注射到l-DOPA致敏大鼠的纹状体中以评估IL-1信号传导对LID的影响。纹状体内IL-1 ra减少LID的表达，而不影响旋转。这些发现表明神经炎症在LID表达中的新作用，并可能涉及使用抗炎剂作为治疗LID的潜在连续疗法。
While the etiology of Parkinson’s disease (PD) remains unknown, there is overwhelming evidence that neuroinflammation plays a critical role in the progressive loss of dopamine (DA) neurons. Because nearly all persons suffering from PD receive l-DOPA, it is surprising that inflammation has not been examined as a potential contributor to the abnormal involuntary movements (AIMs) that occur as a consequence of chronic l-DOPA treatment. As an initial test of this hypothesis, we examined the effects of exogenously administered corticosterone (CORT), an endogenous anti-inflammatory agent, on the expression and development of l-DOPA-induced dyskinesia (LID) in unilateral DA-depleted rats. To do this, male Sprague-Dawley rats received unilateral medial forebrain bundle 6-hydroxydopamine lesions. Three weeks later, l-DOPA primed rats received acute injections of CORT (0–3.75 mg/kg) prior to l-DOPA to assess the expression of LID. A second group of rats was used to examine the development of LID in l-DOPA naïve rats co-treated with CORT and l-DOPA for 2 weeks. AIMs and rotations were recorded. Exogenous CORT dose-dependently attenuated both the expression and development of AIMs without affecting rotations. Real-time RT-PCR of striatal tissue implicated a role for IL-1β in these effects as its expression was increased on the lesioned side in rats treated with l-DOPA (within the DA-depleted striatum) and attenuated with CORT. In the final experiment, IL-1 receptor antagonist (IL-1ra) was microinjected into the striatum of l-DOPA-primed rats to assess the impact of IL-1 signaling on LID. Intrastriatal IL-1ra reduced the expression of LID without affecting rotations. These findings indicate a novel role for neuroinflammation in the expression of LID, and may implicate the use of anti-inflammatory agents as a potential adjunctive therapy for the treatment of LID.
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影响因子：
4.2
作者：
Allan, SM
通讯作者：
Allan, SM
影响因子：
3.2
作者：
Ferri, CC;Ferguson, AV
通讯作者：
Ferguson, AV
影响因子：
6.1
作者：
Cintia Ferrari, Carina;Pott Godoy, Maria Clara;Juan Pitossi, Fernando
通讯作者：
Juan Pitossi, Fernando
影响因子：
3.2
作者：
Barnum, C. J.;Blandino, P., Jr.;Deak, T.
通讯作者：
Deak, T.
影响因子：
6.1
作者：
Arimoto, T;Bing, GY
通讯作者：
Bing, GY