Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia
Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia
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DOI：
10.1016/j.neuropharm.2004.04.003
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发表时间：
2004-08-01
影响因子：
4.7
通讯作者：
Frussa-Filho, R
中科院分区：
文献类型：
--
作者：
Abílio, VC;Silva, RH;Frussa-Filho, R
迟发性运动障碍，最严重的医源性运动障碍，已初步与黑质纹状体多巴胺能超敏反应和氧化应激。也有人认为，长期的精神抑制剂治疗不会引起口腔运动障碍（OD），但与大脑老化的一些底物相互作用，导致OD的过早出现，这可能会随着年龄的增长而自发发生。为了研究黑质纹状体多巴胺超敏性和氧化应激在衰老和利血平诱导的OD中的可能作用，评估了多巴胺能激动剂诱导的刻板行为，多巴胺能纹状体活性的功能指数，以及纹状体抗氧化酶谷胱甘肽过氧化物酶和过氧化氢酶。我们证明，相对于血压正常的Wistar大鼠（NWR），自发性高血压大鼠（SHR）不发展老化或利血平OD。NWR和SHR在刻板行为和纹状体谷胱甘肽过氧化物酶活性方面没有差异。成年和老年SHR呈现较高的纹状体过氧化氢酶活性相对于NWR，和老化增加它只在SHR。过氧化氢酶抑制剂aminotriazole逆转了SHR中衰老和利血平诱导的OD的缺失。我们的研究结果表明，纹状体过氧化氢酶在利血平和衰老诱导的OD的发展中发挥着重要作用。(C)2004爱思唯尔有限公司保留所有权利。
Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD. (C) 2004 Elsevier Ltd. All rights reserved.