@article{ba0e1a0701d54289b8d49d0ee42ed877,
title = "Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models",
abstract = "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 dorsal 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.",
author = "Hutson, {Thomas H.} and Claudia Kathe and Ilaria Palmisano and Kay Bartholdi and Arnau Hervera and {De Virgiliis}, Francesco and Eilidh McLachlan and Luming Zhou and Guiping Kong and Quentin Barraud and Danzi, {Matt C.} and Alejandro Medrano-Fernandez and Lopez-Atalaya, {Jose P.} and Boutillier, {Anne L.} and Sinha, {Sarmistha H.} and Singh, {Akash K.} and Piyush Chaturbedy and Moon, {Lawrence D.F.} and Kundu, {Tapas K.} and Bixby, {John L.} and Lemmon, {Vance P.} and Angel Barco and Gregoire Courtine and Giovanni, {Simone Di}",
note = "Funding Information: We thank M. Scandaglia from the Instituto de Neurociencias (Universidad Miguel Hernandez Consejo Superior de Investigaciones Cient{\'i}ficas Alicante, Spain) for the images of Cre-driven expression of tdTomato in CaMKIIa-positive DRG neurons. We also thank M. Eswaramoorthy, head of the Nanomaterials and Catalysis Laboratory (Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India) for technical assistance with the synthesis of CSP. This work was supported by grants from the Rosetrees Trust (to S.D.G.), Leverhulme Trust (to S.D.G.), The Henry Smith Charity (to S.D.G.), start-up funds from the Division of Brain Sciences, Imperial College London (to S.D.G.), Wings for Life (to S.D.G., T.H.H., and L.D.F.M.), International Spinal Research Trust (to L.D.F.M. and C.K.), the Miami Project to Cure Paralysis (to V.P.L. and J.L.B.), the Walter G. Ross Foundation (to V.P.L. and J.L.B.), the National Institute for Health (NIH; R01 HD057632) (to V.P.L. and J.L.B.), grants from the Spanish Ministry of Economy and Competitivity (MINECO) cofinanced by the European Regional Development Fund (ERDF; SAF2014-56197-R, PCIN-2015-192-C02-01, SEV-2013-0317) (to A.B.), a NARSAD Independent Investigator Grant from the Brain & Behavior Research Foundation (to A.B.), a grant from the Alicia Koplowitz Foundation (to A.B.), a consolidator grant from the European Research Council (ERC-2015-CoG HOW2WALKAGAIN 682999) (to G.C.), the Swiss National Science Foundation (subsidy 310030B_166674 and CRSII3_160696) (to G.C.), and a Sir J C Bose Fellowship (to T.K.K.).",
year = "2019",
month = apr,
day = "10",
doi = "10.1126/scitranslmed.aaw2064",
language = "English (US)",
volume = "11",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "487",
}