Journal Article

Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration

Ruff, Sophie, Duman, Mert, Münger, Emmanuelle, Bochud, Maëlle, Heller, Manfred, Jacob, Claire, Brügger, Valérie

2017

Overview

The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion. Brügger et al . identify part of the molecular machinery that controls Schwann cell development after peripheral nerve injury. Inhibiting HDAC1/2 early after injury enhances nerve regeneration and promotes functional recovery.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/106 / 13/109 / 13/51 / 13/89 / 14/19 / 14/28 / 14/32 / 14/63 / 38/109 / 38/15 / 38/32 / 38/5 / 38/90 / 631/378/1687 / 631/378/2584/1695 / 631/378/2596/3921 / 64/60 / 82/29 / 82/58 / Animals / Axons - drug effects / Axons - metabolism / Benzamides - pharmacology / Driving ability / Early Growth Response Protein 2 - genetics / Early Growth Response Protein 2 - metabolism / Enzymes / Gene Expression Regulation / Genes, Reporter / Genetics / Histone Deacetylase 1 - antagonists & inhibitors / Histone Deacetylase 1 - deficiency / Histone Deacetylase 1 - genetics / Histone Deacetylase 2 - antagonists & inhibitors / Histone Deacetylase 2 - deficiency / Histone Deacetylase 2 - genetics / Histone Deacetylase Inhibitors - pharmacology / Humanities and Social Sciences / JNK Mitogen-Activated Protein Kinases - genetics / JNK Mitogen-Activated Protein Kinases - metabolism / Lesions / Luciferases - genetics / Luciferases - metabolism / Mice / Mice, Knockout / multidisciplinary / Nerve Regeneration - drug effects / Nerve Regeneration - genetics / Nervous system / PAX3 Transcription Factor - genetics / PAX3 Transcription Factor - metabolism / Peripheral Nerve Injuries - drug therapy / Peripheral Nerve Injuries - genetics / Peripheral Nerve Injuries - metabolism / Peripheral Nerve Injuries - pathology / Pyrimidines - pharmacology / Recovery of Function - drug effects / Regrowth / Schwann Cells - drug effects / Schwann Cells - metabolism / Science / Science (multidisciplinary) / Signal Transduction / SOXB1 Transcription Factors - genetics / SOXB1 Transcription Factors - metabolism / Transcription factors / Transcription Factors - genetics / Transcription Factors - metabolism