Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration.,Nature Communications

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Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration.
Nature Communications ( IF 14.7 ) Pub Date : 2017-01-31 , DOI: 10.1038/ncomms14272
Valérie Brügger ₁ , Mert Duman ₁ , Maëlle Bochud ₁ , Emmanuelle Münger ₁ , Manfred Heller ₂ , Sophie Ruff ₁ , Claire Jacob ₁

Affiliation

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.

中文翻译：

延迟组蛋白脱乙酰酶对损伤的反应可加速雪旺细胞修复和神经再生的转化。

周围神经系统（PNS）在受伤后会再生。然而，在大病变的情况下，再生通常会受到损害，轴突重新连接到目标的速度对于成功的功能恢复至关重要。损伤后，成熟的雪旺细胞 (SC) 转化为促进轴突再生的修复细胞，并重新分化以重建髓磷脂。这些过程需要多种转录因子的调节，但其驱动机制仍不完全清楚。在这里，我们确定了由组蛋白脱乙酰酶 2 (HDAC2) 控制的对神经损伤的早期反应，它协调其他染色质重塑酶的作用，诱导 Oct6 的上调，Oct6 是 SC 发育的关键转录因子。使用小鼠遗传学使这种机制失活，可以更早地转化为修复细胞，并导致轴突更快地再生，但会损害髓鞘再生。一致地，损伤后早期的短期 HDAC1/2 抑制剂治疗可加速功能恢复并增强再生，从而确定改善损伤后 PNS 再生的新治疗策略。

更新日期：2017-02-01

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