Document Detail

p53 Regulates the Neuronal Intrinsic and Extrinsic Responses Affecting the Recovery of Motor Function following Spinal Cord Injury.
MedLine Citation:
PMID:  23035104     Owner:  NLM     Status:  In-Data-Review    
Following spinal trauma, the limited physiological axonal sprouting that contributes to partial recovery of function is dependent upon the intrinsic properties of neurons as well as the inhibitory glial environment. The transcription factor p53 is involved in DNA repair, cell cycle, cell survival, and axonal outgrowth, suggesting p53 as key modifier of axonal and glial responses influencing functional recovery following spinal injury. Indeed, in a spinal cord dorsal hemisection injury model, we observed a significant impairment in locomotor recovery in p53(-/-) versus wild-type mice. p53(-/-) spinal cords showed an increased number of activated microglia/macrophages and a larger scar at the lesion site. Loss- and gain-of-function experiments suggested p53 as a direct regulator of microglia/macrophages proliferation. At the axonal level, p53(-/-) mice showed a more pronounced dieback of the corticospinal tract (CST) and a decreased sprouting capacity of both CST and spinal serotoninergic fibers. In vivo expression of p53 in the sensorimotor cortex rescued and enhanced the sprouting potential of the CST in p53(-/-) mice, while, similarly, p53 expression in p53(-/-) cultured cortical neurons rescued a defect in neurite outgrowth, suggesting a direct role for p53 in regulating the intrinsic sprouting ability of CNS neurons. In conclusion, we show that p53 plays an important regulatory role at both extrinsic and intrinsic levels affecting the recovery of motor function following spinal cord injury. Therefore, we propose p53 as a novel potential multilevel therapeutic target for spinal cord injury.
Elisa M Floriddia; Khizr I Rathore; Andrea Tedeschi; Giorgia Quadrato; Anja Wuttke; Jan-Matthis Lueckmann; Kristina A Kigerl; Phillip G Popovich; Simone Di Giovanni
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13956-70     Citation Subset:  IM    
Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, and Graduate School for Cellular and Molecular Neuroscience, University of Tübingen, D-72076 Tübingen, Germany, Axonal Growth and Regeneration Laboratory, German Center for Neurodegenerative Disease, D-53175 Bonn, Germany, and Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio 43210.
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