A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration

in the adult CNS

Myelin is a crucial component of the nervous system that facilitates the transmission of nerve impulses. In the central nervous system (CNS), myelin is produced by oligodendrocytes, while in the peripheral nervous system (PNS), myelin is produced by Schwann cells. Injuries to the CNS often result in the loss of myelin and subsequent impairment of nerve function. In contrast, the PNS has a remarkable ability to regenerate after injury, with Schwann cells playing a key role in this process.

In a recent study published in Nature Neuroscience, researchers investigated the role of histone deacetylase 3 (HDAC3) in peripheral myelin growth and functional regeneration in the adult CNS. HDACs are enzymes that remove acetyl groups from histone proteins, leading to chromatin condensation and gene repression. HDAC3 is known to be involved in the regulation of gene expression in oligodendrocytes and Schwann cells.

The researchers found that HDAC3 plays a critical role in regulating the growth of peripheral myelin and the functional regeneration of injured nerves. Using a mouse model of nerve injury, they showed that HDAC3 is upregulated in Schwann cells after injury and that genetic deletion of HDAC3 in Schwann cells leads to increased myelin growth and improved nerve function.

Further analysis revealed that HDAC3 regulates the expression of key genes involved in myelin growth and nerve function, including Krox20 and Egr2. Krox20 and Egr2 are transcription factors that are essential for Schwann cell differentiation and myelin formation. HDAC3 acts as a negative regulator of Krox20 and Egr2 expression, limiting the growth of peripheral myelin and the functional regeneration of injured nerves.

Overall, this study provides new insights into the molecular mechanisms underlying peripheral myelin growth and functional regeneration in the adult CNS. The findings suggest that targeting HDAC3 could be a promising strategy for promoting myelin growth and nerve function after injury.