PI3-kinase/Akt Pathway-Regulated Membrane Insertion of Acid-Sensing Ion Channel 1a Underlies BDNF-Induced Pain Hypersensitivity
文献类型：期刊论文
| 作者 | Duan, Bo ; Liu, Di-Shi ; Huang, Yu ; Zeng, Wei-Zheng ; Wang, Xiang ; Yu, Hui ; Zhu, Michael X. ; Chen, Zhe-Yu ; Xu, Tian-Le(徐天乐) |
| 刊名 | JOURNAL OF NEUROSCIENCE
 |
| 出版日期 | 2012 |
| 卷号 | 32期号:18页码:6351-6363 |
| ISSN号 | 0270-6474 |
| 关键词 | DORSAL-HORN NEURONS INFLAMMATION-INDUCED HYPERALGESIA PROTEIN-KINASE-C RAT SPINAL-CORD GROWTH-FACTOR-I NEUROTROPHIC FACTOR NMDA RECEPTOR CENTRAL SENSITIZATION NEUROPATHIC PAIN SENSORY NEURONS |
| 通讯作者 | Xu, TL (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Biochem & Mol Cell Biol,Neurosci Div, 280 S Chongqing Rd, Shanghai 200025, Peoples R China,xu-happiness@shsmu.edu.cn |
| 英文摘要 | Central neural plasticity plays a key role in pain hypersensitivity. This process is modulated by brain-derived neurotrophic factor (BDNF) and also involves the type 1a acid-sensing ion channel (ASIC1a). However, the interactions between the BDNF receptor, tropomyosin-related kinase B (TrkB), and ASIC1a are unclear. Here, we show that deletion of ASIC1 gene suppressed the sustained mechanical hyperalgesia induced by intrathecal BDNF application in mice. In both rat spinal dorsal horn neurons and heterologous cell cultures, the BDNF/TrkB pathway enhanced ASIC1a currents via phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB/Akt) cascade and phosphorylation of cytoplasmic residue Ser-25 of ASIC1a, resulting in enhanced forward trafficking and increased surface expression. Moreover, in both rats and mice, this enhanced ASIC1a activity was required for BDNF-mediated hypersensitivity of spinal dorsal horn nociceptive neurons and central mechanical hyperalgesia, a process that was abolished by intrathecal application of a peptide representing the N-terminal region of ASIC1a encompassing Ser-25. Thus, our results reveal a novel mechanism underlying central sensitization and pain hypersensitivity, and reinforce the critical role of ASIC1a channels in these processes. |
| 学科主题 | Neurosciences & Neurology |
| 资助信息 | National Basic Research Program of China[2011CBA00408]; National Natural Science Foundation of China[30830035, 91132303] |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1487]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Duan, Bo,Liu, Di-Shi,Huang, Yu,et al. PI3-kinase/Akt Pathway-Regulated Membrane Insertion of Acid-Sensing Ion Channel 1a Underlies BDNF-Induced Pain Hypersensitivity[J]. JOURNAL OF NEUROSCIENCE,2012,32(18):6351-6363. |
| APA | Duan, Bo.,Liu, Di-Shi.,Huang, Yu.,Zeng, Wei-Zheng.,Wang, Xiang.,...&Xu, Tian-Le.(2012).PI3-kinase/Akt Pathway-Regulated Membrane Insertion of Acid-Sensing Ion Channel 1a Underlies BDNF-Induced Pain Hypersensitivity.JOURNAL OF NEUROSCIENCE,32(18),6351-6363. |
| MLA | Duan, Bo,et al."PI3-kinase/Akt Pathway-Regulated Membrane Insertion of Acid-Sensing Ion Channel 1a Underlies BDNF-Induced Pain Hypersensitivity".JOURNAL OF NEUROSCIENCE 32.18(2012):6351-6363. |
入库方式： OAI收割
来源：上海神经科学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。