Glutamate receptor 1 phosphorylation at serine 845 contributes to the therapeutic effect of olanzapine on schizophrenia-like cognitive impairments
文献类型：期刊论文
| 作者 | Zhang C1,2; Fang YR[*]3; Xu L[*]2 |
| 刊名 | SCHIZOPHRENIA RESEARCH
 |
| 出版日期 | 2014 |
| 卷号 | 159期号:2-3页码:376-384 |
| 关键词 | Antipsychotics Synaptic plasticity Morris water maze Glutamate receptor |
| 通讯作者 | yirufang@aliyun.com ; lxu@vip.163.com |
| 合作状况 | 其它 |
| 英文摘要 | Schizophrenia patients exhibit a wide range of impairments in cognitive functions. Clinically, atypical antipsychotic drugs (AAPs) such as olanzapine (OLZ) have a therapeutic effect on memory function among schizophrenia patients rather than typical antipsychotics, e. g., haloperidol. To date, however, little is known about the neuroplasticity mechanism underlying the effect of AAPs on the impairment of cognitive functions. Here, we treated schizophrenia rat models with a systematic injection of MK-801 (0.1 mg/kg) and chose the drug OLZ as a tool to investigate the mechanisms of AAPs when used to alter cognitive function. The results showed that the systematic administration of MK-801 results in the impairment of spatial learning and memory as well as spatial working memory in a Morris water maze task. OLZ but not HAL improved these MK-801-induced cognitive dysfunctions. After MK-801 application, the hippocampal LTP was profoundly impaired. In conjunction with the results of the behavioral test, the administration of OLZ but not of HAL resulted in a significant reversal effect on the impaired LTP induced via MK-801 application. Furthermore, we found that OLZ but not HAL can upregulate the phosphorylation of GluR1 Ser845. These data suggest that the therapeutic effect of OLZ on cognitive dysfunctions may be due to its contribution to synaptic plasticity via the ability to upregulate the state of GluR1 Ser845 phosphorylation. We therefore suggest that the upregulated state of GluR1 Ser845 phosphorylation may be a promising target for developing novel therapeutics for treating schizophrenia. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by the National Natural Science Foundation of China (81000581 and 81471358), 973 program from theMinistryof Science and Technol- ogy of China (2013CB835103), Shanghai Science & Technology Development Foundation (12140904200) and National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH2011-873). |
| 语种 | 英语 |
| 公开日期 | 2014-12-19 |
| 源URL | [http://159.226.149.42:8088/handle/152453/8197]  |
| 专题 | 昆明动物研究所_学习记忆的分子神经机制 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_分子病理学 |
| 作者单位 | 1.Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 3.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China |
| 推荐引用方式 GB/T 7714 | Zhang C,Fang YR[*],Xu L[*]. Glutamate receptor 1 phosphorylation at serine 845 contributes to the therapeutic effect of olanzapine on schizophrenia-like cognitive impairments[J]. SCHIZOPHRENIA RESEARCH,2014,159(2-3):376-384. |
| APA | Zhang C,Fang YR[*],&Xu L[*].(2014).Glutamate receptor 1 phosphorylation at serine 845 contributes to the therapeutic effect of olanzapine on schizophrenia-like cognitive impairments.SCHIZOPHRENIA RESEARCH,159(2-3),376-384. |
| MLA | Zhang C,et al."Glutamate receptor 1 phosphorylation at serine 845 contributes to the therapeutic effect of olanzapine on schizophrenia-like cognitive impairments".SCHIZOPHRENIA RESEARCH 159.2-3(2014):376-384. |
入库方式： OAI收割
来源：昆明动物研究所
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