Unraveling roundworm nerve regeneration mechanism could aid nerve injury treatment

October 4, 2016
Regenerating neurons in C. elegans. Credit: Nagoya University

Nagoya University researchers clarify detailed molecular mechanisms behind regrowth of severed nerves in roundworms; could lead to treatments promoting human recovery from nerve injury.

Certain types of , such as those from automobile accidents and falls, can damage or sever the axons that connect neurons and allow them to communicate with each other. Although axons elsewhere in the body can regenerate to some extent after such damage, those in nerves are far less capable, resulting in long-lasting or permanent impairment. Treating such injuries requires clarification of how certain nerves are induced to regenerate and which molecular pathways are involved. By studying regeneration in roundworms, Nagoya University researchers have discovered another signaling pathway that induces nerves to regenerate. The team also showed that this pathway is the same as the one that leads to identification and subsequent clearance of dying cells.

Neurons communicate with each other via electrical signals conveyed through dendrites and axons. This connectivity within the nerve is a source of the multiple functions of this organ, but damage to these connections due to trauma can cause functional impairment. Nerve regeneration after nerve injury is therefore an issue of special interest, but is difficult to study in humans. A non-parasitic, free-living roundworm nematode is a useful model for studying this issue as it avoids the ethical problems associated with human experimentation and its short generation time and simple development facilitate genetic engineering experiments.

To shed light on how damaged nerves are induced to regenerate, the researchers investigated various strains of this worm in which different genes were mutated or inactivated. They subjected the worms to a range of experiments, including labeling nerves with a fluorescent marker, cutting the nerves with a laser, and then monitoring their regrowth under a microscope. They also examined the worms' resistance with different genetic backgrounds to heavy metal stress, based on earlier findings that similar genes may be involved in both resistance to heavy metal exposure and . When certain proteins encoded by these genes were absent or dysfunctional in the worms, their nerves were less able to regenerate, particularly during adulthood. They were also less able to endure exposure to a toxic level of copper. By comparing these results among the strains in which single or multiple genes had been inactivated, the researchers established a complex molecular pathway that allows nerves to regenerate. They also found that the key molecular machinery involved in this is the same as that by which dying cells are recognized, engulfed by immune system cells, and disposed of.

"Many of the molecules and mechanisms we identified in worms have equivalents in humans," corresponding author Naoki Hisamoto says. "Our findings should therefore lead us to targets in humans that we can use to improve recovery after nerve injury by promoting regrowth of damaged axons."

Explore further: Study finds a key to nerve regeneration

More information: S. I. Pastuhov et al. The Core Molecular Machinery Used for Engulfment of Apoptotic Cells Regulates the JNK Pathway Mediating Axon Regeneration in Caenorhabditis elegans, Journal of Neuroscience (2016). DOI: 10.1523/JNEUROSCI.0453-16.2016

Related Stories

Study finds a key to nerve regeneration

September 14, 2016

Researchers at the University of Wisconsin–Madison have found a switch that redirects helper cells in the peripheral nervous system into "repair" mode, a form that restores damaged axons.

Zebrafish reveal how axons regenerate on a proper path

November 5, 2015

When peripheral nerves are damaged and their vital synaptic paths are disrupted, they have the ability to regenerate and reestablish lost connections. But what about when a nerve is severed completely, its original route ...

New approach to spinal cord and brain injury research

July 15, 2015

Many an injury will heal, but the damaged spinal cord is notoriously recalcitrant. There's new hope on the horizon, though. A team of researchers led by the University of South Carolina's Jeff Twiss just reported an innate ...

Recommended for you

Study finds gray matter density increases during adolescence

May 26, 2017

For years, the common narrative in human developmental neuroimaging has been that gray matter in the brain - the tissue found in regions of the brain responsible for muscle control, sensory perception such as seeing and hearing, ...

Researchers identify brain network organization changes

May 25, 2017

As children age into adolescence and on into young adulthood, they show dramatic improvements in their ability to control impulses, stay organized, and make decisions. Those executive functions of the brain are key factors ...

Scientists demonstrate the existence of 'social neurons'

May 25, 2017

The existence of new "social" neurons has just been demonstrated by scientists from the Institut de neurosciences des systèmes (Aix-Marseille University / INSERM), the Laboratoire de psychologie sociale et cognitive (Université ...

How fear can develop out of others' traumas

May 25, 2017

What happens in the brain when we see other people experiencing a trauma or being subjected to pain? Well, the same regions that are involved when we feel pain ourselves are also activated when we observe other people who ...

Babies' slow brain waves could predict problems

May 25, 2017

The brain waves of healthy newborns – which appear more abnormal than those of severe stroke victims – could be used to accurately predict which babies will have neurodevelopmental disorders.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.