Injury-induced activation of the endocannabinoid system promotes axon regeneration

Sara Martinez-Torres; Francina Mesquida-Veny; José Antonio Del Rio; Arnau Hervera

doi:10.1016/j.isci.2023.106814

Injury-induced activation of the endocannabinoid system promotes axon regeneration

iScience. 2023 May 5;26(6):106814. doi: 10.1016/j.isci.2023.106814. eCollection 2023 Jun 16.

Authors

Sara Martinez-Torres^{1

2

3

4}, Francina Mesquida-Veny^{1

2

3

4}, José Antonio Del Rio^{1

2

3

4}, Arnau Hervera^{1

2

3

4

5

6}

Affiliations

¹ Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.
² Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona, Spain.
³ Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, Ministry of Economy and Competitiveness, Madrid, Spain.
⁴ Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
⁵ Clinical Neuroimmunology Group, Vall Hebron Research Institute (VHIR), Barcelona, Spain.
⁶ Multiple Sclerosis Centre of Catalonia (CEM-CAT), Barcelona, Spain.

Abstract

Regeneration after a peripheral nerve injury still remains a challenge, due to the limited regenerative potential of axons after injury. While the endocannabinoid system (ECS) has been widely studied for its neuroprotective and analgesic effects, its role in axonal regeneration and during the conditioning lesion remains unexplored. In this study, we observed that a peripheral nerve injury induces axonal regeneration through an increase in the endocannabinoid tone. We also enhanced the regenerative capacity of dorsal root ganglia (DRG) neurons through the inhibition of endocannabinoid degradative enzyme MAGL or a CB1R agonist. Our results suggest that the ECS, via CB1R and PI3K-pAkt pathway activation, plays an important role in promoting the intrinsic regenerative capacity of sensory neurons after injury.

Keywords: Clinical neuroscience; Drugs; Molecular medicine.