Frontiers in Cellular Neuroscience (Feb 2018)
Netrin-1 Promotes Synaptic Formation and Axonal Regeneration via JNK1/c-Jun Pathway after the Middle Cerebral Artery Occlusion
- Mouwei Zheng,
- Mouwei Zheng,
- Mouwei Zheng,
- Ronghua Chen,
- Ronghua Chen,
- Ronghua Chen,
- Hongbin Chen,
- Hongbin Chen,
- Hongbin Chen,
- Yixian Zhang,
- Yixian Zhang,
- Yixian Zhang,
- Jianhao Chen,
- Jianhao Chen,
- Jianhao Chen,
- Peiqiang Lin,
- Peiqiang Lin,
- Peiqiang Lin,
- Quan Lan,
- Quan Lan,
- Quan Lan,
- Qilin Yuan,
- Qilin Yuan,
- Qilin Yuan,
- Yongxing Lai,
- Yongxing Lai,
- Yongxing Lai,
- Xinhong Jiang,
- Xinhong Jiang,
- Xinhong Jiang,
- Xiaodong Pan,
- Xiaodong Pan,
- Nan Liu,
- Nan Liu,
- Nan Liu,
- Nan Liu
Affiliations
- Mouwei Zheng
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Mouwei Zheng
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Mouwei Zheng
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Ronghua Chen
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Ronghua Chen
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Ronghua Chen
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Hongbin Chen
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Hongbin Chen
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Hongbin Chen
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Yixian Zhang
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Yixian Zhang
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Yixian Zhang
- Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, China
- Jianhao Chen
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Jianhao Chen
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Jianhao Chen
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Peiqiang Lin
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Peiqiang Lin
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Peiqiang Lin
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Quan Lan
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Quan Lan
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Quan Lan
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Qilin Yuan
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Qilin Yuan
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Qilin Yuan
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Yongxing Lai
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Yongxing Lai
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Yongxing Lai
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Xinhong Jiang
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Xinhong Jiang
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Xinhong Jiang
- Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, China
- Xiaodong Pan
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Xiaodong Pan
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Nan Liu
- Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China
- Nan Liu
- Institute of Cerebral Vascular Disease of Fujian Province, Fuzhou, China
- Nan Liu
- Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
- Nan Liu
- Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, China
- DOI
- https://doi.org/10.3389/fncel.2018.00013
- Journal volume & issue
-
Vol. 12
Abstract
As a secreted axon guidance molecule, Netrin-1 has been documented to be a neuroprotective factor, which can reduce infarct volume, promote angiogenesis and anti-apoptosis after stroke in rodents. However, its role in axonal regeneration and synaptic formation after cerebral ischemic injury, and the related underlying mechanisms remain blurred. In this study, we used Adeno-associated vectors carrying Netrin-1 gene (AAV-NT-1) to up-regulate the expression level of Netrin-1 in rats’ brain after middle cerebral artery occlusion (MCAO). We found that the up-regulated level of Netrin-1 and its receptor DCC promoted axonal regeneration and synaptic formation; the overexpression of Netrin-1 activated the JNK1 signaling pathway; these effects were partially reduced when JNK1 signaling pathway was inhibited by SP600125 (JNK specific inhibitor). Taken together, these findings suggest that Netrin-1 can facilitate the synaptic formation and axonal regeneration via the JNK1 signaling pathway after cerebral ischemia, thus promoting the recovery of neural functions.
Keywords