title: Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice.
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.
authors: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors: Xiaosong
authors: X
authors: He
authors: Yaning
authors: Y
authors: Li
authors: Haiyan
authors: H
authors: Lu
authors: Zhijun
authors: Z
authors: Zhang
authors: Yongting
authors: Y
authors: Wang
authors: Guo-Yuan
authors: GY
authors: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics*; D000075388:Netrin-1; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1
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