Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit
Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit
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铜宗诱导的小鼠脱髓鞘：与年龄相关的脆弱性和探索行为缺陷
DOI：
10.1007/s12264-013-1323-1
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发表时间：
2013-04
影响因子：
5.6
通讯作者：
Xiao, Lan
中科院分区：
文献类型：
--
作者：
Wang, Hongkai;Li, Chengren;Wang, Hanzhi;Mei, Feng;Liu, Zhi;Shen, Hai-Ying;Xiao, Lan
精神分裂症是一种精神疾病，主要影响年轻人（15至35岁），但其病因在很大程度上仍不明确。近年来，越来越多的证据表明，少突胶质细胞的脱髓鞘和/或功能障碍是其发病机制的一个重要特征。我们假设年轻人易发生脱髓鞘可能是导致精神分裂症的原因。在本研究中，三个不同年龄组的小鼠，即幼年（3周），成年（6周）和中年（8个月），进行了6周的饮食含有0.2%的cuprizone（CPZ），以创建急性脱髓鞘的动物模型。然后，年龄相关的脆弱性CPZ诱导的脱髓鞘，行为结果，髓鞘相关的分子生物学变化进行了评估。我们证明了：（1）与中年小鼠相比，CPZ治疗导致幼年和成年小鼠胼胝体（与精神分裂症的病理生理学密切相关的区域）更严重的脱髓鞘：（2）幼年和成年小鼠更高水平的脱髓鞘与髓鞘碱性蛋白的更大程度的减少、CC-1阳性成熟少突胶质细胞的更多损失和更高水平的星形胶质细胞活化相关;（3）CPZ处理导致幼年和成年小鼠比中年小鼠更明显的探索行为缺陷。总之，我们的数据表明，年龄相关的脱髓鞘与并发行为缺陷的脆弱性，提供支持证据，更好地了解年轻人的精神分裂症的发病易感性。
Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined. Recently, accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis. We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia. In the present study, three different age cohorts of mice, i.e. juvenile (3 weeks), young-adult (6 weeks) and middle-aged (8 months), were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination. Then, age-related vulnerability to CPZ-induced demyelination, behavioral outcomes, and myelination-related molecular biological changes were assessed. We demonstrated: (1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum, a region closely associated with the pathophysiology of schizophrenia; (2) the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein, more loss of CC-1-positive mature oligodendrocytes, and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice. Together, our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit, providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.
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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
影响因子：
4.5
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
通讯作者：
He, Jue
DOI：
10.1111/j.1750-3639.2011.00501.x
发表时间：
2012-01
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Kim S;Steelman AJ;Zhang Y;Kinney HC;Li J
通讯作者：
Li J
DOI：
--
发表时间：
2010-10
期刊：
JPMA. The Journal of the Pakistan Medical Association
影响因子：
--
作者：
I. Naqvi;M. Murtaza;M. R. Nazir;H. Naqvi
通讯作者：
I. Naqvi;M. Murtaza;M. R. Nazir;H. Naqvi
影响因子：
5.3
作者：
Sim, FJ;Zhao, C;Franklin, RJM
通讯作者：
Franklin, RJM
影响因子：
5.7
作者：
Kubicki, M;Park, H;Shenton, ME
通讯作者：
Shenton, ME