Neuronal plasticity after spinal cord injury: identification of a gene cluster driving neurite outgrowth.
Functional recovery after spinal cord injury (SCI) may result in part from axon outgrowth and related plasticity through coordinated changes at the molecular level. We employed microarray analysis to identify a subset of genes the expression patterns of which were temporally coregulated and correlated to functional recovery after SCI. Steady-state mRNA levels of this synchronously regulated gene cluster were depressed in both ventral and dorsal horn neurons within 24 h after injury, followed by strong re-induction during the following 2 wk, which paralleled functional recovery. The identified cluster includes neuritin, attractin, microtubule-associated protein 1a, and myelin oligodendrocyte protein genes. Transcriptional and protein regulation of this novel gene cluster was also evaluated in spinal cord tissue and in single neurons and was shown to play a role in axonal plasticity. Finally, in vitro transfection experiments in primary dorsal root ganglion cells showed that cluster members act synergistically to drive neurite outgrowth.
Di Giovanni
Simone
S
Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
Faden
Alan I
AI
Yakovlev
Alexander
A
Duke-Cohan
Jonathan S
JS
Finn
Tom
T
Thouin
Melissa
M
Knoblach
Susan
S
De Biase
Andrea
A
Bregman
Barbara S
BS
Hoffman
Eric P
EP
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000378:metabolism; D019922:GAP-43 Protein; D005727:Ganglia, Spinal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics*; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000235:genetics*; D016501:Neurites / Q000737:chemistry* / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
C492191:Atrn protein, rat; D019922:GAP-43 Protein; C093429:MAP1A protein, human; C571326:MOG protein, human; C490546:Map1a protein, rat; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger