A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity
A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity
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DOI：
10.1016/j.expneurol.2009.01.010
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发表时间：
2009-05-01
影响因子：
5.3
通讯作者：
Calabresi, Paolo
中科院分区：
文献类型：
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作者：
Belcastro, Vincenzo;Tozzi, Alessandro;Calabresi, Paolo
腺苷A2A受体已成为帕金森病（PD）实验药物治疗的一个有吸引力的非多巴胺能靶点。此外，已经假设A2A腺苷受体拮抗剂在PD和进行性核上性麻痹（PSP）的实验模型中发挥神经保护作用。有趣的是，在这两种病理条件下，线粒体复合物I的缺陷已被发现。因此，利用细胞外和细胞内记录从皮质纹状体脑切片，我们已经测试了可能的神经保护作用的两个A2A受体拮抗剂，STI 535和ZM 241385，对不可逆的电生理效应诱导的鱼藤酮急性应用，作为线粒体复合物I活性的选择性抑制剂的杀虫剂。这两种拮抗剂减少鱼藤酮引起的皮质纹状体场电位振幅的损失，以及这种毒素对纹状体棘神经元引起的膜去极化。A2A受体拮抗剂的使用可能是一个有前途的神经保护策略，在基底神经节疾病涉及的线粒体复合物I活性的赤字。(C)2009 Elsevier Inc. All rights reserved.
Adenosine A2A receptor has emerged as an attractive non-dopaminergic target in the experimental pharmacological therapy for Parkinson's disease (PD). Moreover, it has been postulated that A2A adenosine receptor antagonists exert neuroprotective effects in experimental models of PD and progressive supranuclear palsy (PSP). Interestingly, in both these pathological conditions a deficit of mitochondrial complex I has been found. Thus, utilizing extracellular and intracellular recordings from corticostriatal brain slices, we have tested the possible neuroprotective action of two A2A receptor antagonists, STI535 and ZM241385, on the irreversible electrophysiological effects induced by the acute application of rotenone, a pesticide acting as a selective inhibitor of mitochondrial complex I activity. Both these antagonists reduced the rotenone-induced loss of corticostriatal field potential amplitude as well as the membrane depolarization caused by this toxin on striatal spiny neurons. The use of A2A receptor antagonists might represent a promising neurciprotective strategy in basal ganglia disorders involving a deficit of mitochondrial complex I activity. (C) 2009 Elsevier Inc. All rights reserved.