Abstract
Restoration of lost function following a nervous system injury is limited in adulthood as the regenerative capacity of nervous system declines with age. Pharmacological approaches have not been very successful in alleviating the consequences of nervous system injury. On the contrary, physical activity and rehabilitation interventions are often beneficial to improve the health conditions in the patients with neuronal injuries. Using touch neuron circuit of Caenorhabditis elegans, we investigated the role of physical exercise in the improvement of functional restoration after axotomy. We found that a swimming session of 90 minutes following the axotomy of Posterior Lateral Microtubule (PLM) neuron can improve functional recovery in larval and adult stage animals. In older age, multiple exercise sessions were required to enhance the functional recovery. Genetic analysis of axon regeneration mutants showed that exercise-mediated enhancement of functional recovery depends on the ability of axon to regenerate. Exercise promotes early initiation of regrowth, self-fusion of proximal and distal ends, as well as post-regrowth enhancement of function. We further found that the swimming exercise promotes axon regeneration through the activity of cellular energy sensor AAK-2/AMPK in both muscle and neuron. Our study established a paradigm where systemic effects of exercise on functional regeneration could be addressed at the single neuron level.
Significance Statement
Accelerating axonal regeneration and subsequent functional restoration is a major challenge to the people with nervous system injury. Research on rodents and humans suggests that rehabilitation therapy helps regain the lost function after neuronal injury. The nematode C. elegans provides an advantage to investigate the role of exercise in facilitating the axonal regeneration at the level of single neuron. Our study shows that swimming exercise promotes functional restoration via structural and functional changes in injured mechanosensory neuron. The benefit of exercise in regeneration depends on the metabolic energy sensor AAK-2/AMPK. This study provides a molecular perspective to exercise-mediated enhancement of axon regeneration.
Footnotes
Authors report no conflict of interest.
This work is supported by the NBRC core fund from the Department of Biotechnology, The India Alliance DBT Wellcome (Grant # IA/I/13/1/500874) and a grant from Science and Engineering Research Board (SERB: CRG/2019/002194). S.K was supported by the SERB- National Post-doctoral Fellowship scheme (NPDF) (SERB File Number: PDF/2017/001610).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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