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, Jose P. Lopez-Atalaya, Anne L. Boutillier, Sarmistha H. Sinha, Akash K. Singh, Piyush Chaturbedy, Lawrence D.F. Moon, Tapas K. Kundu, John BixbyVance Lemmon, Angel Barco, Gregoire Courtine, Simone Di Giovanni

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbereaaw2064
JournalScience Translational Medicine
Volume11
Issue number487
DOIs
StatePublished - Apr 10 2019

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Acetylation
Spinal Cord Injuries
Histones
Axons
Regeneration
Rodentia
Carrier Proteins
Neuronal Plasticity
Wounds and Injuries
Spinal Ganglia
Epigenomics
Electric Stimulation
Rehabilitation
Central Nervous System
Gene Expression
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hutson, T. H., Kathe, C., Palmisano, I., Bartholdi, K., Hervera, A., De Virgiliis, F., ... Giovanni, S. D. (2019). Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models. Science Translational Medicine, 11(487), [eaaw2064]. https://doi.org/10.1126/scitranslmed.aaw2064

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

In: Science Translational Medicine, Vol. 11, No. 487, eaaw2064, 10.04.2019.

Research output: Contribution to journalArticle

Hutson, TH, Kathe, C, Palmisano, I, Bartholdi, K, Hervera, A, De Virgiliis, F, McLachlan, E, Zhou, L, Kong, G, Barraud, Q, Danzi, MC, Medrano-Fernandez, A, Lopez-Atalaya, JP, Boutillier, AL, Sinha, SH, Singh, AK, Chaturbedy, P, Moon, LDF, Kundu, TK, Bixby, J, Lemmon, V, Barco, A, Courtine, G & Giovanni, SD 2019, 'Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models', Science Translational Medicine, vol. 11, no. 487, eaaw2064. https://doi.org/10.1126/scitranslmed.aaw2064
Hutson, Thomas H. ; Kathe, Claudia ; Palmisano, Ilaria ; Bartholdi, Kay ; Hervera, Arnau ; De Virgiliis, Francesco ; McLachlan, Eilidh ; Zhou, Luming ; Kong, Guiping ; Barraud, Quentin ; Danzi, Matt C. ; Medrano-Fernandez, Alejandro ; Lopez-Atalaya, Jose P. ; Boutillier, Anne L. ; Sinha, Sarmistha H. ; Singh, Akash K. ; Chaturbedy, Piyush ; Moon, Lawrence D.F. ; Kundu, Tapas K. ; Bixby, John ; Lemmon, Vance ; Barco, Angel ; Courtine, Gregoire ; Giovanni, Simone Di. / Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models. In: Science Translational Medicine. 2019 ; Vol. 11, No. 487.
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