GM-CSF inhibits apoptosis of neural cells via regulating the expression of apoptosis-related proteins

Xian Huang, Jung Kyoung Choi, So Ra Park, Yoon Ha, Hyeonseon Park, Seung Hwan Yoon, Hyung Chun Park, Jong Oon Park, Byung Hyune Choi

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Abstract

Recently, we reported that GM-CSF showed therapeutic effects on the spinal cord injury (SCI) in rat model possibly via its anti-apoptotic activity in the nervous system. This study investigated the molecular mechanism of its anti-apoptotic and neuroprotective effects in N2a neuroblastoma cells and in rat SCI model. GM-CSF inhibited staurosporine-induced cytotoxicity and apoptosis of N2a cells. Single administration of GM-CSF either intraperitoneally or locally using a gelfoam, clearly reduced the apoptotic events in the surrounding region of the injury site in rat SCI model. Immunohistochemical analysis showed that apoptosis of cells occurred mainly in the neurons, but not significantly in the astrocytes in the surrounding regions. In both N2a cells and in rat SCI model, GM-CSF actually reduced the expression of pro-apoptotic proteins (p53, p21WAF1/CIP1 and Bax), while further induced that of an anti-apoptotic protein (Bcl-2). In the Basso-Beattie-Bresnahan (BBB) locomotor test, the single GM-CSF administration showed better behavioral recovery than the untreated control only at early times within 1 week after injury. Overall, GM-CSF was shown to exert its neuroprotective effect on the neural injury by regulating the expression of apoptosis related genes, providing the molecular basis on its anti-apoptotic activity. Longer administration of GM-CSF appeared to be necessary for the sustained functional recovery from SCI.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalNeuroscience Research
Volume58
Issue number1
DOIs
Publication statusPublished - 2007 May 1

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Huang, X., Choi, J. K., Park, S. R., Ha, Y., Park, H., Yoon, S. H., Park, H. C., Park, J. O., & Choi, B. H. (2007). GM-CSF inhibits apoptosis of neural cells via regulating the expression of apoptosis-related proteins. Neuroscience Research, 58(1), 50-57. https://doi.org/10.1016/j.neures.2007.01.015