The sphingosine-1-phosphate analogue, FTY-720, promotes the proliferation of embryonic neural stem cells, enhances hippocampal neurogenesis and learning and memory abilities in adult mice
文献类型：期刊论文
| 作者 | Sun, Yili; Hong, Feng; Zhang, Lei; Feng, Linyin
|
| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2016-09 |
| 卷号 | 173期号:18页码:2793-2807 |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/bph.13557 |
| 文献子类 | Article |
| 英文摘要 | Background and purposeFingolimod (FTY-720) is the first oral therapeutic drug approved for the relapsing-remitting forms of multiple sclerosis. Neural stem cells (NSCs) are capable of continuous self-renewal and differentiation. The dentate gyrus of the hippocampus in the adult mammalian brain contains a population of NSCs and is one of the regions where neurogenesis takes place. FTY-720 has been shown to have neuroprotective effects in several model systems, so we investigated the direct effects of FTY-720 on NSCs and adult neurogenesis. Experimental approachesWe assessed the effects of FTY-720 on the proliferation and differentiation of cultured embryonic hippocampal NSCs using the 5-bromo-2-deoxyuridine incorporation assay, the neurosphere formation assay and western blot analysis. Receptor selective agonists and antagonists were used to identify the mechanisms involved. Neurogenesis in the hippocampus of C57BL/6 mice was also assessed by immunohistochemistry. The Morris water maze and fear conditioning tests were used to detect the learning and memory abilities of mice. Key resultsFTY-720 promoted the proliferation of embryonic hippocampal NSCs probably via the activation of ERK signalling, G(i/o) proteins and S1P(1) receptors. However, FTY-720 did not affect the differentiation of cultured hippocampal NSCs. In vivo, chronic treatment with FTY-720 promoted hippocampal neurogenesis in adult C57BL/6 mice and enhanced their learning and memory abilities. Conclusions and ImplicationsOur results suggest a new target for the activation of NSCs and provide an insight into the therapeutic effects of FTY-720 in neuropsychiatric disorders, neurodegenerative diseases and age-related cognitive decline where hippocampal neurogenesis is compromised. |
| WOS关键词 | SPHINGOSINE 1-PHOSPHATE ; PROGENITOR CELLS ; CONCISE GUIDE ; MULTIPLE-SCLEROSIS ; ALZHEIMERS-DISEASE ; FTY720 FINGOLIMOD ; WATER-MAZE ; IN-VIVO ; RECEPTORS ; NEURONS |
| 资助项目 | Scientific Innovation Project of the Chinese Academy of Sciences[XDA 01040304] ; National Natural Science Foundation of China[81123004] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | WILEY-BLACKWELL |
| WOS记录号 | WOS:000383259000008 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275918]  |
| 专题 | 药理学第二研究室 国家新药筛选中心 |
| 通讯作者 | Feng, Linyin |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Yili,Hong, Feng,Zhang, Lei,et al. The sphingosine-1-phosphate analogue, FTY-720, promotes the proliferation of embryonic neural stem cells, enhances hippocampal neurogenesis and learning and memory abilities in adult mice[J]. BRITISH JOURNAL OF PHARMACOLOGY,2016,173(18):2793-2807. |
| APA | Sun, Yili,Hong, Feng,Zhang, Lei,&Feng, Linyin.(2016).The sphingosine-1-phosphate analogue, FTY-720, promotes the proliferation of embryonic neural stem cells, enhances hippocampal neurogenesis and learning and memory abilities in adult mice.BRITISH JOURNAL OF PHARMACOLOGY,173(18),2793-2807. |
| MLA | Sun, Yili,et al."The sphingosine-1-phosphate analogue, FTY-720, promotes the proliferation of embryonic neural stem cells, enhances hippocampal neurogenesis and learning and memory abilities in adult mice".BRITISH JOURNAL OF PHARMACOLOGY 173.18(2016):2793-2807. |
入库方式： OAI收割
来源：上海药物研究所
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