Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice:: Protective effect of α-lipoic acid

Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice:: Protective effect of α-lipoic acid
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DOI:
10.1016/j.bbr.2006.11.013
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发表时间:
2007-02-12
影响因子:
2.7
通讯作者:
Anzai, Kazunori
Anzai, Kazunori
中科院分区:
心理学3区
文献类型:
--
作者:
Manda, Kailash;Ueno, Megumi;Anzai, Kazunori

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活性氧与神经变性和认知障碍有关,这是由于神经元组织的易感性较高。小脑最近被报道参与认知功能。因此,本研究旨在探讨α -硫辛酸对辐射诱导的氧化应激和小脑抗氧化状态的作用及其与认知功能障碍的相关性。利用热释电红外传感器和程控视频跟踪系统分别观察小鼠的自发运动活动和空间记忆任务。全身x射线照射(6 Gy)对小鼠的参考记忆和运动活动有明显损害。然而,在照射前用α -硫辛酸对小鼠进行急性腹腔治疗可显著减轻这种认知功能障碍。α -硫辛酸预处理对辐射诱导的小鼠小脑蛋白质羰基和硫代巴比妥酸活性物质(TBARS)的增加具有非常高的保护作用。此外,α -硫辛酸预处理还能抑制辐射诱导的小脑总巯基、非蛋白巯基和蛋白结合巯基(T-SH、NP-SH、PB-SH)含量和血浆铁还原能力(FRAP)的下降。此外,α -硫辛酸处理小鼠的小脑细胞结构完整,完整的浦肯野细胞和颗粒细胞数量高于未处理小鼠。结果清楚地表明-硫辛酸是有效的神经保护抗氧化剂。(c) 2006 Elsevier B.V.版权所有
Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher Vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role alpha-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated Such cognitive dysfunction. alpha-Lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Moreover, alpha-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that alpha-lipoic acid is potent neuroprotective antioxidant. (c) 2006 Elsevier B.V. All rights reserved.