Abstract
NF-κB is a ubiquitous nuclear transcription factor that regulates a number of physiological processes. NF-κB activity has been implicated in enhancing neuronal survival following CNS injury. The present study was conducted to test the hypothesis that NF-κB activity is up-regulated in neurons of the spinal cord in response to peripheral nerve transection. In this series of experiments, we used NF-κB reporter mice in which activation of NF-κB drives the expression of the lac-z gene. The response to injury of cells in the spinal cord was assessed by evaluating the number and distribution of β-galalactosidase (β-gal)-positive cells following sciatic nerve transection. The animals were randomly assigned to four groups, which were allowed to survive for one, three, five and ten days. Four mice that did not undergo sciatic nerve transection were assigned to each group to serve as controls. The total number of β-gal-positive cells in the right and left dorsal and ventral horns were compared. The numbers of β-gal-positive cells between the right and left sides were significantly different three and five days post axotomy (p<0.05). Double immunofluorescent labeling was utilized to characterize which cells showed NF-κB activity, and it revealed that all β-gal-positive cells were colocalized with MAP-2-positive neurons. The results of this study demonstrated that complete sciatic nerve transection leads to an up-regulation of NF-κB transactivation in spinal neurons ipsilateral to the side of transection. The increase in activity in the ipsilateral dorsal horn is consistent with this transcription factor acting as neuronal survival signal during this time frame in response to the peripheral nerve insult.
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Acknowledgments
We wish to thank Lucy Colina and Dr. Cheryl Kassed for help with immunohistochemistry. This work was supported by the American Heart Association grant 0355183B (SS) and National Institute of Neurological Diseases and Stroke NS39141-01A2 (KRP).
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Pollock, G., Pennypacker, K., Mémet, S. et al. Activation of NF-κB in the mouse spinal cord following sciatic nerve transection. Exp Brain Res 165, 470–477 (2005). https://doi.org/10.1007/s00221-005-2318-6
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DOI: https://doi.org/10.1007/s00221-005-2318-6