Imperial College London
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ProfessorSimoneDi Giovanni

Faculty of Medicine, Department of Brain Sciences

James W Harnett Chair in Restorative Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 3178s.di-giovanni

 
 
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Location

 

E505Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hutson:2019:10.1126/scitranslmed.aaw2064,
author = {Hutson, TH and Kathe, C and Palmisano, I and Bartholdi, K and Hervera, A and De, Virgiliis F and Mclachlan, E and Zhou, L and Kong, G and Barraud, Q and Danzi, MC and Medrano-Fernandez, A and Lopez-Atalaya, JP and Boutillier, AL and Sinha, SH and Singh, AK and Chaturbedy, P and Moon, LDF and Kundu, TK and Bixby, JL and Lemmon, VP and Barco, A and Courtine, G and Di, Giovanni S},
doi = {10.1126/scitranslmed.aaw2064},
journal = {Science Translational Medicine},
title = {Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models},
url = {http://dx.doi.org/10.1126/scitranslmed.aaw2064},
volume = {11},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Hutson,TH
AU  - Kathe,C
AU  - Palmisano,I
AU  - Bartholdi,K
AU  - Hervera,A
AU  - De,Virgiliis F
AU  - Mclachlan,E
AU  - Zhou,L
AU  - Kong,G
AU  - Barraud,Q
AU  - Danzi,MC
AU  - Medrano-Fernandez,A
AU  - Lopez-Atalaya,JP
AU  - Boutillier,AL
AU  - Sinha,SH
AU  - Singh,AK
AU  - Chaturbedy,P
AU  - Moon,LDF
AU  - Kundu,TK
AU  - Bixby,JL
AU  - Lemmon,VP
AU  - Barco,A
AU  - Courtine,G
AU  - Di,Giovanni S
DO  - 10.1126/scitranslmed.aaw2064
PY  - 2019///
SN  - 1946-6234
TI  - Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models
T2  - Science Translational Medicine
UR  - http://dx.doi.org/10.1126/scitranslmed.aaw2064
UR  - http://hdl.handle.net/10044/1/70137
VL  - 11
ER  -
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