Mice study explores how nerve cells repair themselves

New research in mouse models by scientists at The Ohio State University Wexner Medical Center, School of Medicine and Imperial College London explored how nerve cells repair themselves, which could lead to new treatments for nerve damage.

Researchers have studied how the 3D structure of nerve cells’ DNA affects their ability to heal after injury. Their results are published in the Proceedings of the National Academy of Sciences.

“We discovered that certain loops of DNA, called promoter-enhancer loops, are important for activating genes that help nerves regrow. These loops are held together by a protein complex called cohesin.

“When this protein is missing, DNA loops do not form properly and nerves cannot heal properly,” said study first author and co-investigator Ilaria Palmisano, Ph.D., an assistant professor at Ohio State Department of Neuroscience. and Department of Plastic and Reconstructive Surgery.

Palmisano carried out the work at Imperial College London with co-investigator Professor Simone Di Giovanni, MD, PhD, of Imperial’s Department of Brain Sciences, and others, including scientists from the University of Miami.

The ability of neurons to regenerate in the peripheral nervous system depends in part on the activation of regenerative genes. This results in the synthesis of new proteins needed to repair injured nerves.

“Chromatin, which is the ‘instruction manual’ of each cell, is tightly folded inside the cell nucleus. How it unfolds or ‘opens’ when activated impacts how it functions. how instructions are ‘read’ and interpreted by cells,” said the study’s lead researcher, Di Giovanni, who holds a chair in restorative neuroscience at Imperial College.

Their previous research in mice had shown that the activation of regenerative genes is affected by chromatin organization. To induce repair of injured nerves, the neurons’ chromatin must be opened, Palmisano said.

The team’s current research in mice has revealed another aspect of chromatin organization that is essential for the repair of injured nerves.

“We know that chromatin is organized into a complex structure, made up of three-dimensional domains (genomic regions) within which the chromatin is folded into loops,” Palmisano said. “These loops allow contact between ‘genomic sites’ that are distant from each other in the linear genomic sequence. These contact points are crucial because they enable communication between genes and their regulatory sequences, called ‘enhancers,’ resulting in an increase in gene activity.”

Researchers have discovered that after damage to the peripheral nervous system, specific contacts form between specific regenerative genes and specific enhancers in neurons.

“Our study has broad implications for neuronal biology and suggests new avenues for novel repair strategies,” Palmisano said. “Future directions will be to understand how the protein cohesin is activated after nerve injury. This way, we can further activate cohesin to promote regeneration in conditions where it is low or absent, such as in the central nervous system.”