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

DOI
https://doi.org/10.3389/fncel.2018.00013
Journal volume & issue
Vol. 12

Abstract

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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.

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