Activation of NF-kappaB in the mouse spinal cord following sciatic nerve transection.
NF-kappaB is a ubiquitous nuclear transcription factor that regulates a number of physiological processes. NF-kappaB activity has been implicated in enhancing neuronal survival following CNS injury. The present study was conducted to test the hypothesis that NF-kappaB activity is up-regulated in neurons of the spinal cord in response to peripheral nerve transection. In this series of experiments, we used NF-kappaB reporter mice in which activation of NF-kappaB 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 beta-galalactosidase (beta-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 beta-gal-positive cells in the right and left dorsal and ventral horns were compared. The numbers of beta-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-kappaB activity, and it revealed that all beta-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-kappaB 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.
Pollock
G
G
Department of Anatomy, Health Sciences Center, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa 33612, USA.
Pennypacker
K R
KR
Mémet
S
S
Israël
A
A
Saporta
S
S
D000818:Animals; D000870:Anterior Horn Cells / Q000201:enzymology / Q000378:metabolism; D019771:Axotomy; D002452:Cell Count; D003714:Denervation; D005455:Fluorescent Antibody Technique; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020671:Posterior Horn Cells / Q000201:enzymology / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D001616:beta-Galactosidase