Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse
Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse
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喹硫平减轻 C57BL/6 小鼠大脑中铜宗诱导的白质病理
DOI：
10.1016/j.schres.2008.09.013
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发表时间：
2008-12
影响因子：
4.5
通讯作者：
He, Jue
中科院分区：
文献类型：
--
作者：
Li, Xin-Min;Jiang, Wengao;Li, Xiaokun;Xiao, Lan;Yan, Bin;Wang, Yanlin;Bi, Xiaoying;Kong, Jiming;Xu, Haiyun;Zhang, Yanbo;He, Jue
最近使用新的磁共振成像技术和微阵列分析的人类研究表明，精神分裂症是一种脑部疾病，伴有白质(WM)的变化，白质主要由少突胶质细胞(OL)及其突起包裹在神经元轴突周围组成。为了研究OLs在精神分裂症的病理生理学和治疗中的假定作用，动物实验是必不可少的。在本研究中，C57BL/6小鼠在饲料中加入0.2%的铜试剂(CPZ)，连续5周，在此期间饮用蒸馏水，不加或加奎硫平(QTP，10 mg/kg)。以普通饲料喂养的小鼠为对照。CPZ是一种铜络合剂，已有报道通过特异性损伤OL诱导C57BL/6小鼠脑内持续脱髓鞘。QTP是一种非典型的抗精神病药物，广泛用于治疗精神分裂症和其他精神障碍。与之前的研究一致，暴露于CPZ的小鼠表现出普遍的髓鞘破坏和脱髓鞘。免疫印迹分析显示，CPZ暴露后大鼠大脑皮层髓鞘碱性蛋白(MBP)含量减少。此外，脱髓鞘部位充斥着激活的小胶质细胞和星形胶质细胞，但也有少量髓鞘形成的OL。此外，暴露于CPZ的小鼠大脑皮层铜锌超氧化物歧化酶活性降低。然而，在联合服用QTP的CPZ暴露的小鼠中，所有这些WM的病理变化要么被预防，要么被缓解。这些结果表明，CPZ暴露的C57BL/6小鼠是一种潜在的动物模型，可以研究OLS在精神分裂症发病和治疗中的可能作用。
Recent human studies employing new magnetic resonance imaging techniques and micro-array analyses feature schizophrenia as a brain disease with alterations in white matter (WM), which is mainly composed of oligodendrocytes (OLs) and their processes wrapping around neuronal axons. To examine the putative role of OLs in the pathophysiology and treatment of schizophrenia, animal studies are essential. In the present study, C57BL/6 mice were given 0.2% cuprizone (CPZ) in their diet for five weeks during which they drank distilled water without or with quetiapine (QTP, 10 mg/kg). The mice fed with normal chow were used as controls. CPZ is a copper chelator and has been reported to induce consistent demyelination in the brain of C57BL/6 mouse by specifically damaging OLs. QTP is an atypical antipsychotic widely used in the treatment of schizophrenia and other psychotic disorders. In accordance with previous studies, CPZ-exposed mice showed pervasive myelin breakdown and demyelination. The amount of myelin basic protein (MBP) in the cerebral cortex was decreased by CPZ-exposure as shown in Western-blot analysis. In addition, the demyelinated sites were teemed with activated microglia and astrocytes but a few myelin forming OLs. Moreover, the activity of copper-zinc superoxide dismutase decreased in the cerebral cortex of CPZ-exposed mice. However, all of these pathological changes in WM were either prevented or alleviated in CPZ-exposed mice co-administered with QTP. These results suggest that the CPZ-exposed C57BL/6 mouse is a potential animal model to study possible roles of OLs in the pathogenesis and treatment of schizophrenia.
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影响因子：
4.7
作者：
G. Venturini
通讯作者：
G. Venturini
影响因子：
4.5
作者：
V. Vostrikov;N. Uranova;D. Orlovskaya
通讯作者：
V. Vostrikov;N. Uranova;D. Orlovskaya
影响因子：
17.7
作者：
Lang, DJ;Kopala, LC;Honer, WG
通讯作者：
Honer, WG
影响因子：
6.9
作者：
Cheung, V.;Cheung, C.;Chua, S. E.
通讯作者：
Chua, S. E.
影响因子：
2.3
作者：
Christensen, J;Holcomb, J;Garver, DL
通讯作者：
Garver, DL