| Autor: |
Saunders NR; Department of Pharmacology & Therapeutics, The University of Melbourne, Victoria, Australia., Noor NM; Department of Pharmacology & Therapeutics, The University of Melbourne, Victoria, Australia., Dziegielewska KM; Department of Pharmacology & Therapeutics, The University of Melbourne, Victoria, Australia., Wheaton BJ; Department of Pharmacology & Therapeutics, The University of Melbourne, Victoria, Australia., Liddelow SA; Department of Pharmacology & Therapeutics, The University of Melbourne, Victoria, Australia; Department of Neurobiology, Stanford University, Stanford, California, United States of America., Steer DL; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia., Ek CJ; Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden., Habgood MD; Department of Pharmacology & Therapeutics, The University of Melbourne, Victoria, Australia., Wakefield MJ; Walter & Eliza Hall Institute of Medical Research, Victoria, Australia; Department of Genetics, The University of Melbourne, Victoria, Australia., Lindsay H; Walter & Eliza Hall Institute of Medical Research, Victoria, Australia; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland., Truettner J; The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, Miami, Florida, United States of America., Miller RD; Center for Evolutionary & Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America., Smith AI; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia., Dietrich WD; The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, Miami, Florida, United States of America. |
| Abstrakt: |
This study describes a combined transcriptome and proteome analysis of Monodelphis domestica response to spinal cord injury at two different postnatal ages. Previously we showed that complete transection at postnatal day 7 (P7) is followed by profuse axon growth across the lesion with near-normal locomotion and swimming when adult. In contrast, at P28 there is no axon growth across the lesion, the animals exhibit weight-bearing locomotion, but cannot use hind limbs when swimming. Here we examined changes in gene and protein expression in the segment of spinal cord rostral to the lesion at 24 h after transection at P7 and at P28. Following injury at P7 only forty genes changed (all increased expression); most were immune/inflammatory genes. Following injury at P28 many more genes changed their expression and the magnitude of change for some genes was strikingly greater. Again many were associated with the immune/inflammation response. In functional groups known to be inhibitory to regeneration in adult cords the expression changes were generally muted, in some cases opposite to that required to account for neurite inhibition. For example myelin basic protein expression was reduced following injury at P28 both at the gene and protein levels. Only four genes from families with extracellular matrix functions thought to influence neurite outgrowth in adult injured cords showed substantial changes in expression following injury at P28: Olfactomedin 4 (Olfm4, 480 fold compared to controls), matrix metallopeptidase (Mmp1, 104 fold), papilin (Papln, 152 fold) and integrin α4 (Itga4, 57 fold). These data provide a resource for investigation of a priori hypotheses in future studies of mechanisms of spinal cord regeneration in immature animals compared to lack of regeneration at more mature stages. |
