Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice |
| |
| Authors: | Xiaosong He Yaning Li Haiyan Lu Zhijun Zhang Yongting Wang Guo-Yuan Yang |
| |
| Affiliation: | 1.Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China;2.Department of Neurology, Shanghai First People''s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;3.Department of Neurology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China |
| |
| Abstract: | Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral tests. Proliferated oligodendrocyte progenitor cells (OPCs), newly matured oligodendrocytes, and remyelination were semi-quantified by immunohistochemistry. The role of NT-1 in oligodendrogenesis was further explored by examining specific NT-1 receptors and their function. Netrin-1 overexpression was detected in neurons and astrocytes 2 weeks after AAV-NT-1 gene transfer and significantly improved the neurobehavioral outcomes compared with the control (P<0.05). In comparison with the control, proliferated OPCs, newly matured oligodendrocytes, and remyelination were greatly increased in the ipsilateral hemisphere of AAV-NT-1-transduced mice. Furthermore, both NT-1 receptors deleted in colorectal carcinoma and UNC5H2 were expressed on OPCs whereas only UNC5H2 was expressed in myelinated axons. Our study indicated that NT-1 promoted OPC proliferation, differentiation, and increased remyelination, suggesting that NT-1 is a promising factor for white matter repairing and remodeling after ischemia. |
| |
| Keywords: | ischemia netrin-1 oligodendrocyte progenitor cells remyelination white matter |
|
|
