Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD
文献类型：期刊论文
| 作者 | Zhang, Bing1,2,3; Guo, Fei3; Ma, Yuqin2,3; Song, Yingcai1; Lin, Rong1; Shen, Fu-Yi1; Jin, Guo-Zhang3 ; Li, Yang3; Liu, Zhi-Qiang1
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| 刊名 | SCIENTIFIC REPORTS
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| 出版日期 | 2017-06-19 |
| 卷号 | 7 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-017-03680-2 |
| 文献子类 | Article |
| 英文摘要 | Major depressive disorder (MDD) is a common neuropsychiatric disorder characterized by diverse symptoms. Although several antidepressants can influence dopamine system in the medial prefrontal cortex (mPFC), but the role of D1R or D2R subtypes of dopamine receptor during anti-depression process is still vague in PFC region. To address this question, we investigate the antidepressant effect of levo-stepholidine (l-SPD), an antipsychotic medication with unique pharmacological profile of D1R agonism and D2R antagonism, and clarified its molecular mechanisms in the mPFC. Our results showed that l-SPD exerted antidepressant-like effects on the Sprague-Dawley rat CMS model of depression. Mechanism studies revealed that l-SPD worked as a specific D1R agonist, rather than D2 antagonist, to activate downstream signaling of PKA/mTOR pathway, which resulted in increasing synaptogenesis-related proteins, such as PSD 95 and synapsin I. In addition, l-SPD triggered long-term synaptic potentiation (LTP) in the mPFC, which was blocked by the inhibition of D1R, PKA, and mTOR, supporting that selective activation of D1R enhanced excitatory synaptic transduction in PFC. Our findings suggest a critical role of D1R/PKA/mTOR signaling cascade in the mPFC during the l-SPD mediated antidepressant process, which may also provide new insights into the role of mesocortical dopaminergic system in antidepressant effects. |
| WOS关键词 | MAJOR DEPRESSIVE DISORDER ; D-1 DOPAMINE-RECEPTORS ; CHRONIC MILD STRESS ; SYNAPTIC PLASTICITY ; D1 RECEPTOR ; SUCROSE CONSUMPTION ; CEREBROSPINAL-FLUID ; FRONTAL-CORTEX ; IN-VIVO ; MTOR |
| 资助项目 | China National Natural Science Foundation[31200771] ; China National Natural Science Foundation[31171011] ; China National Natural Science Foundation[31371066] ; Shanghai Key Laboratory of Psychotic Disorders[13DZ2260500] ; Ministry of Science and Technology[2013CB91060101] ; Science and Technology Commission of Shanghai Municipality[16411967400] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040214] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000403650300052 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272601]  |
| 专题 | 院士及顾问专家 药理学第二研究室 |
| 通讯作者 | Jin, Guo-Zhang; Li, Yang; Liu, Zhi-Qiang |
| 作者单位 | 1.Tongji Univ, Sch Med, Shanghai Matern & Infant Hosp 1, Dept Anesthesiol, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Bing,Guo, Fei,Ma, Yuqin,et al. Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD[J]. SCIENTIFIC REPORTS,2017,7. |
| APA | Zhang, Bing.,Guo, Fei.,Ma, Yuqin.,Song, Yingcai.,Lin, Rong.,...&Liu, Zhi-Qiang.(2017).Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD.SCIENTIFIC REPORTS,7. |
| MLA | Zhang, Bing,et al."Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD".SCIENTIFIC REPORTS 7(2017). |
入库方式： OAI收割
来源：上海药物研究所
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