Related Experiment Video
Updated: May 17, 2025

Contusion Spinal Cord Injury via a Microsurgical Laminectomy in the Regenerative Axolotl
Published on: October 20, 2019
The endocannabinoid system regulates both ependymoglial and neuronal cell responses to a tail amputation in the
Michael Tolentino1, Sarah E Walker1,2, Gaynor E Spencer1
1Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
Background:
The endocannabinoid system is a neuromodulatory system implicated in cellular processes during both development and regeneration. The Mexican axolotl, one of only a few vertebrates capable of central nervous system regeneration, was used to examine the role of the endocannabinoid system in the regeneration of the tail and spinal cord following amputation.
Results:
The endocannabinoid receptor CB1 was upregulated in the regenerating axolotl spinal cord by 4 hours following tail amputation, and this upregulation persisted for at least 14 days. The endocannabinoid receptor CB2 was upregulated later, between 7 and 14 days after tail amputation. Both CB1 and CB2 were located in ependymoglia and neurons within the regenerating spinal cord. Treatment with inverse agonists to inhibit CB1 (AM251) or CB2 (AM630) inhibited spinal cord and tail regeneration. During the first 7 days after injury, CB1 and CB2 expression was also necessary for the proliferation of ependymoglial cells and the regeneration of axons into the newly regenerated tail tissue. However, only CB1 was necessary for the differentiation of ependymoglia into immature neurons.
Conclusions:
These studies are the first to examine the role of the endocannabinoid system during spinal cord regeneration in a regeneration-competent vertebrate.

