ABSTRACT
<p><b>BACKGROUND</b>The Ras/Raf/ERK1/2 signaling pathway controls many cellular responses such as cell proliferation, migration, differentiation, and death. In the nervous system, emerging evidence also points to a death-promoting role for ERK1/2 in both in vitro and in vivo models of neuronal death. To further investigate how Ras/Raf/ERK1/2 up-regulation may lead to the development of spinal cord injury, we developed a cellular model of Raf/ERK up-regulation by overexpressing c-Raf in cultured spinal cord neurons (SCNs) and dorsal root ganglions (DRGs).</p><p><b>METHODS</b>DRGs and SCNs were prepared from C57BL/6J mouse pups. DRGs or SCNs were infected with Ad-Raf-1 or Ad-Null adenovirus alone. Cell adhesion assay and cell migration assay were investigated, DiI labeling was employed to examine the effect of the up-regulation of Ras/Raf/ERK1/2 signaling on the dendritic formation of spinal neurons. We used the TO-PRO-3 staining to examine the apoptotic effect of c-Raf on DRGs or SCNs. The effect on the synapse formation of neurons was measured by using immunofluorescence.</p><p><b>RESULTS</b>We found that Raf/ERK up-regulation stimulates the migration of both SCNs and DRGs, and impairs the formation of excitatory synapses in SCNs. In addition, we found that Raf/ERK up-regulation inhibits the development of mature dendritic spines in SCNs. Investigating the possible mechanisms through which Raf/ERK up-regulation affects the excitatory synapse formation and dendritic spine development, we discovered that Raf/ERK up-regulation suppresses the development and maturation of SCNs.</p><p><b>CONCLUSION</b>The up-regulation of the Raf/ERK signaling pathway may contribute to the pathogenesis of spinal cord injury through both its impairment of the SCN development and causing neural circuit imbalances.</p>
Subject(s)
Animals , Female , Mice , Pregnancy , Cell Movement , Physiology , Dendritic Spines , Metabolism , Physiology , Ganglia, Spinal , Cell Biology , MAP Kinase Signaling System , Physiology , Neurogenesis , Genetics , Physiology , Neurons , Cell Biology , Signal Transduction , Genetics , Physiology , Spinal Cord , Cell Biology , Synapses , Metabolism , Physiology , Up-Regulation , raf Kinases , Genetics , Metabolism , ras Proteins , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To review the recent studies about human umbilical cord mesenchymal stem cells (hUCMSCs) and advances in the treatment of spinal cord injury. Data sources Published articles (1983 - 2007) about hUCMSCs and spinal cord injury were selected using Medline. Study selection Articles selected were relevant to development of mesenchymal stem cells (MSCs) for transplantation in spinal cord injury therapy. Of 258 originally identified articles 51 were selected that specifically addressed the stated purpose.</p><p><b>RESULTS</b>Recent work has revealed that hUCMSCs share most of the characteristics with MSCs derived from bone marrow and are more appropriate to transplantation for cell based therapies.</p><p><b>CONCLUSIONS</b>Human umbilical cord could be regarded as a source of MSCs for experimental and clinical needs. In addition, as a peculiar source of stem cells, hUCMSCs may play an important role in the treatment of spinal cord injury.</p>