Internet Archive Scholar

Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models

Thomas H. Hutson, Claudia Kathe, Ilaria Palmisano, Kay Bartholdi, Arnau Hervera, Francesco De Virgiliis, Eilidh McLachlan, Luming Zhou, Guiping Kong, Quentin Barraud, Matt C. Danzi, Alejandro Medrano-Fernandez (+12 others)
2019 Science Translational Medicine  

Preserved Fulltext

fulltext thumbnail
Web Archive Capture PDF (3.0 MB)
https://web.archive.org/web/20200305092207/https://univoak.eu/islandora/object/islandora%3A84541/datastream/PDF/view

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL. The file type is application/pdf.

After a spinal cord injury, axons fail to regenerate in the adult mammalian central nervous system, leading to permanent deficits in sensory and motor functions. Increasing neuronal activity after an injury using electrical stimulation or rehabilitation can enhance neuronal plasticity and result in some degree of recovery; however, the underlying mechanisms remain poorly understood. We found that placing mice in an enriched environment before an injury enhanced the activity of proprioceptive
more » ... sal root ganglion neurons, leading to a lasting increase in their regenerative potential. This effect was dependent on Creb-binding protein (Cbp)–mediated histone acetylation, which increased the expression of genes associated with the regenerative program. Intraperitoneal delivery of a small-molecule activator of Cbp at clinically relevant times promoted regeneration and sprouting of sensory and motor axons, as well as recovery of sensory and motor functions in both the mouse and rat model of spinal cord injury. Our findings showed that the increased regenerative capacity induced by enhancing neuronal activity is mediated by epigenetic reprogramming in rodent models of spinal cord injury. Understanding the mechanisms underlying activity-dependent neuronal plasticity led to the identification of potential molecular targets for improving recovery after spinal cord injury.
doi:10.1126/scitranslmed.aaw2064 pmid:30971452 fatcat:v5gh336edzf4jprjfruytklexm
Citation

Thomas H. Hutson, Claudia Kathe, Ilaria Palmisano, Kay Bartholdi, Arnau Hervera, Francesco De Virgiliis, Eilidh McLachlan, Luming Zhou, Guiping Kong, Quentin Barraud, Matt C. Danzi, Alejandro Medrano-Fernandez, Jose P. Lopez-Atalaya, Anne L. Boutillier, Sarmistha H. Sinha, Akash K. Singh, Piyush Chaturbedy, Lawrence D. F. Moon, Tapas K. Kundu, John L. Bixby, Vance P. Lemmon, Angel Barco, Gregoire Courtine, Simone Di Giovanni. "Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models." Science Translational Medicine 11.487 (2019) eaaw2064