In vivo and in vitro characterization of novel neuronal plasticity factors identified following spinal cord injury.
Following spinal cord injury, there are numerous changes in gene expression that appear to contribute to either neurodegeneration or reparative processes. We utilized high density oligonucleotide microarrays to examine temporal gene profile changes after spinal cord injury in rats with the goal of identifying novel factors involved in neural plasticity. By comparing mRNA changes that were coordinately regulated over time with genes previously implicated in nerve regeneration or plasticity, we found a gene cluster whose members are involved in cell adhesion processes, synaptic plasticity, and/or cytoskeleton remodeling. This group, which included the small GTPase Rab13 and actin-binding protein Coronin 1b, showed significantly increased mRNA expression from 7-28 days after trauma. Overexpression in vitro using PC-12, neuroblastoma, and DRG neurons demonstrated that these genes enhance neurite outgrowth. Moreover, RNAi gene silencing for Coronin 1b or Rab13 in NGF-treated PC-12 cells markedly reduced neurite outgrowth. Coronin 1b and Rab13 proteins were expressed in cultured DRG neurons at the cortical cytoskeleton, and at growth cones along with the pro-plasticity/regeneration protein GAP-43. Finally, Coronin 1b and Rab13 were induced in the injured spinal cord, where they were also co-expressed with GAP-43 in neurons and axons. Modulation of these proteins may provide novel targets for facilitating restorative processes after spinal cord injury.
Di Giovanni
Simone
S
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. sd69@georgetown.edu
De Biase
Andrea
A
Yakovlev
Alexander
A
Finn
Tom
T
Beers
Jeanette
J
Hoffman
Eric P
EP
Faden
Alan I
AI
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005727:Ganglia, Spinal / Q000378:metabolism; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D005810:Multigene Family; D009473:Neuronal Plasticity; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D020691:rab GTP-Binding Proteins / Q000235:genetics
D017931:DNA Primers; D008840:Microfilament Proteins; C072061:coronin proteins; D020691:rab GTP-Binding Proteins