Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK Pathway

• Main Authors: Jianhao Chen, Houwei Du, Yixian Zhang, Hongbin Chen, Mouwei Zheng, Peiqiang Lin, Quan Lan, Qilin Yuan, Yongxing Lai, Xiaodong Pan, Ronghua Chen, Nan Liu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-12-01
• Series: Frontiers in Cellular Neuroscience
• Subjects: Netrin-1; primary cortical neurons; DNA damage; DCC; ERK; OGD
• Online Access: http://journal.frontiersin.org/article/10.3389/fncel.2017.00387/full

In the nervous system, Netrin-1 serves as a neural guide, mediating the neuronal development. However, it remains blurred whether Netrin-1 can protect neurons from apoptosis induced by cerebral stroke. In the current study, the cultured rat primary cortical neurons were transfected with Netrin-1-encoding lentivirus before the oxygen-glucose-deprivation (OGD) treatment. Cell death and apoptosis were evaluated by lactate dehydrogenase (LDH) release and flow cytometry. We found that Netrin-1 attenuated OGD-induced cell death and neuronal apoptosis at 24 h after OGD treatment, and that the overexpression of Netrin-1 activated the ERK signaling pathway. These effects were partly abolished by blocking its receptor deleted in colorectal cancer (DCC) or U0126, an inhibitor of the ERK signaling pathway. Netrin-1 overexpression in neurons elevated the expression of DCC, on mRNA level and protein level. Netrin-1 also reduced DNA damage. Taken together, our findings suggest that Netrin-1 attenuates cell death and neuronal apoptosis via the DCC/ERK signaling pathway in the cultured primary cortical neurons after OGD injury, which may involve the mediation of DNA damage in the neurons.