Chilean research behind the fingerprint of peripheral nervous system regeneration

The peripheral nervous system allows us to receive stimuli from the environment and respond to them appropriately, for example, through muscle contraction that allows our coordinated movement.

Based on data collected in the United States, it is estimated that one in 350 people suffers from injuries to the peripheral nervous system caused by both accidents and compression injuries to the nerves due to repetitive movements. Motor function is also affected by different pathologies, both motor (such as amyotrophic lateral sclerosis) and non-motor (such as HIV and diabetes), or due to chemotherapy in cancer patients.

Even though medicine has made great strides in restoring motor function through microsurgical techniques, nerve transplants, and rehabilitation strategies, regeneration of the peripheral system in humans is still very inefficient, with the consequent deterioration in the quality of life of patients suffering from these conditions. That is why this is a very active area of ​​research.

Motor neurons located in the spinal cord control the contraction of muscles through a very precise point of contact, called the neuromuscular synapse. Although many peripheral nerve conditions end up damaging this synapse, research in this field has focused on repairing nerve injuries at the site of damage, under the assumption that this will rescue motor function.

However, “investigations in recent years have shown that even if the repair of damaged nerves has been improved, this is not always accompanied by a successful recovery of mobility, which is why our group has focused on studying a relatively less-attended aspect: the regeneration of the neuromuscular synapse”, pointed out the Dr. Henriquez.

The study, led by PhD researcher Francisca Bermedo Garcia and carried out in collaboration with the Dr. Lucia Tabaresa Spanish researcher expert in neuromuscular physiology, characterized the cellular changes that occur after degenerative damage (without repair) and compared them with those that occur when there is regeneration of the neuromuscular synapse.

As a result of this comparison, the research group identified specific traits that only occur in regeneration and that persist over time, so they could represent the fingerprint of how the neuromuscular synapse adapts to enable successful recovery of motor function.

Paradigm shift

A particularly noteworthy aspect is that several of the characteristic features of regeneration identified in this study correspond to cellular changes that have traditionally been associated with conditions of impaired motor innervation, such as accidents, pathologies and aging. One of these traits is “fragmentation,” where damage to the neuromuscular synapse results in a shift in the distribution of its cellular components toward a shape that resembles a bunch of grapes.

In this regard, the detailed study of Dr. Henríquez’s group demonstrated, for the first time, that there are two types of fragmentation of the neuromuscular synapse, which are differentiated by the different levels of stability of their components and, therefore, in its potential ability to promote successful regeneration.

“The search for possible interventions that allow us in some way to transform the synapses fragmented by damage into those that we find specifically in the regenerative model is one of the interesting alternatives with therapeutic potential that our study opens up”, concluded Henríquez