A novel flavanone derivative ameliorates cuprizone-induced behavioral changes and white matter pathology in the brain of mice
A novel flavanone derivative ameliorates cuprizone-induced behavioral changes and white matter pathology in the brain of mice
复制标题
一种新型黄烷酮衍生物可改善铜宗诱导的小鼠大脑行为变化和白质病理学
DOI：
10.1016/j.psychres.2017.07.075
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发表时间：
2017-11-01
影响因子：
11.3
通讯作者：
Li, Lin
中科院分区：
文献类型：
--
作者：
Sun, Zheng-yu;Gu, Hong-shun;Li, Lin
近年来的研究表明，白色物质病变在精神分裂症的发病机制中起重要作用。DHF-6是本实验室合成的一种新的黄烷酮衍生物。本研究的目的是研究DHF-6对0.2%铜唑酮喂养的C57 BL/6小鼠模型的行为变化和白色病理学的影响。结果表明，铜腙可使大鼠Y迷宫实验中的自发性改变减少，旷场实验中的自发活动增加，电镜下观察到脱髓鞘，髓鞘碱性蛋白（MBP）表达下降，少突胶质前体细胞（OPCs）向成熟少突胶质细胞（OLs）分化减少，以及通过蛋白质印迹和/或免疫细胞化学分析测量的胼胝体中小胶质细胞和星形胶质细胞的活化。灌胃给予DHF-6（25和50 mg/kg）5周可增加自发性交替，减少自发活动，逆转脱髓鞘和MBP下降，促进OPCs向成熟OL分化，抑制小胶质细胞和星形胶质细胞的活化。提示DHF-6可能通过促进髓鞘再生和抑制神经炎症，减轻白色损害，从而改善精神分裂症患者的认知功能障碍和阳性症状，对精神分裂症的治疗有一定的临床意义。
Recent studies have shown that white matter lesions play an important role in the pathogenesis of schizophrenia. DHF-6 is a novel flavanone derivative synthesized in our laboratory. The purpose of the present study was to investigate the effects of DHF-6 on behavioral changes and white matter pathology in a 0.2% cuprizone-fed C57BL/6 mice model. The results showed that cuprizone induced a decrease in spontaneous alternations in the Y-maze test, an increase in locomotor activity in the open field test, demyelination determined by electron microscopy, a decline in the expression of myelin basic protein (MBP), a decrease in the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), and an activation of microglia and astrocytes in the corpus callosum measured by western blot and/or immunocytochemical analyses. Intragastric administration of DHF-6 (25 and 50 mg/kg) for 5-weeks increased the spontaneous alternations, reduced locomotor activity, reversed demyelination and MBP decrease, promoted OPCs differentiation into mature OLs, and inhibited the activation of microglia and astrocytes. These results suggest that DHF-6 may improve cognitive impairment and the positive symptoms of schizophrenia by alleviating white matter lesions via facilitating remyelination and inhibiting neuroinflammation, thus may be beneficial in the treatment of schizophrenia.