Injury-induced activation of the endocannabinoid system promotes axon regeneration

Martínez-Torres, Sara; Mesquida-Veny, Francina; Río, José Antonio del; Hervera, Arnau

doi:10.1016/j.isci.2023.106814

Cited by 3 publications

(3 citation statements)

References 48 publications

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“… 18 , 24 CB 1 receptors are also involved in axonal regeneration after injury. 25 At the same time, CB 1 receptors are expressed on ADMSCs, 26 and they are involved in maintaining cell viability and metabolic activity. 27 CB 1 receptors also direct toward the differentiation of MSCs in the bone marrow and adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

The role of cannabinoid CB1 receptors in the antinociceptive and reparative actions of mesenchymal stem cells in rats with peripheral neuropathic pain

Yerofeyeva,

Pinchuk,

Rjabceva

et al. 2023

Ibrain

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Mesenchymal stem cells (MSCs) can produce antinociceptive and reparative effects. Presumably, the MSCs‐induced antinociception may be partly due to the involvement of the endocannabinoid system. The study aimed to evaluate the antinociceptive and reparative effects of adipose‐derived MSCs (ADMSCs) upon pharmacological modulation of cannabinoid CB1 receptor in peripheral tissues or on ADMSCs' membranes in a rat model of peripheral neuropathy. ADMSCs were injected into the area of rat sciatic nerve injury (i) with no additional treatments, (ii) at the tissue CB1 receptor activation by endogenous agonist anandamide (AEA) or blockade with a selective AM251 antagonist; and (iii) preincubated with AEA or AM251. The evaluation of CB1 receptor activity involved analyzing nociceptive responses, gait parameters, and histology. Transplantation of ADMSCs upon activation of CB1 receptors, both on AMSCs' membranes or in the area of nerve injury, accelerated the analgesia and recovery of dynamic gait parameters, abolished static gait disturbances, and promoted the fastest nerve regeneration. Only blockade of CB1 receptors on ADMSCs shortened ADMSCs‐induced analgesia and decreased the number of preserved nerve fibers. CB1 receptors on ADMSCs significantly contribute to their pain‐relieving and tissue‐repairing capabilities by stimulating the growth factors secretion and suppressing the release of pro‐inflammatory cytokines. Peripheral CB1 receptors do not significantly influence ADMSC‐induced antinociception.

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Section: Discussionmentioning

confidence: 99%

The role of cannabinoid CB1 receptors in the antinociceptive and reparative actions of mesenchymal stem cells in rats with peripheral neuropathic pain

Yerofeyeva,

Pinchuk,

Rjabceva

et al. 2023

Ibrain

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“…Despite an impressive amount of knowledge of the diverse effects of CB1Rs on axonal growth in CNS, its roles in the PNS and at the NMJ are ill defined, limiting our knowledge on the sensory system and its potential therapeutic use is exclusively in the treatment of neuropathic pain [4][5][6] , also associated to nerve injury [7][8][9] . Here, we investigated if the PSCs' ability to regulate nerve repair response could be mediated by CB1R and, thus, its selective activation influences NMJs reinnervation.…”

Section: Cb1r Expression Has Been Found At Neuromuscular Junctions (N...mentioning

confidence: 99%

“…Also, efficient pharmacological treatments are not available and often solely targeting pain-related relief 1,3 . One of the possible targets is the Endocannabinoid system (EC), known to be present on the sensory system and used in the treatment of neuropathic pain [4][5][6] , also associated with nerve injury [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid type-1 (CB₁) receptors in glial cells promote neuromuscular junction repair following nerve injury

Piovesana,

Charron,

Arbour

et al. 2024

Preprint

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Cannabinoids are frequently used in the treatment of neuropathic pain related to nerve injury. However, despite evidence for their roles in the regulation of axonal guidance and synapse formation during development of the central nervous system (CNS), their possible involvement in response to peripheral nerve injury remains poorly defined and the knowledge of its role is mostly related to the peripheral sensory system. Following nerve injury, contemporary to axonal repair, massive morphological and functional changes reshape synaptic elements at neuromuscular junctions (NMJs) aiming to promote their reinnervation. This process is mediated in part by Perisynaptic Schwann cells (PSCs), glial cells at the NMJ essential for its maintenance and repair. Here we investigated the novel role of Cannabinoid type-1 receptor (CB1R) at NMJ, in particular on PSCs, during motor nerve recovery following nerve injury. Using morphological analysis, we studied the consequences of CB1R pharmacological and genetic blockade following denervation and reinnervation in adult NMJs. CB1R blockade caused an acceleration of the denervation process followed by a great delay in reinnervation as indicated by a significant percentage of denervated NMJs, accompanied by a decrease of mono- and poly-innervated NMJs. Remarkably, a similar phenomenon was observed when CB1R is selectively knocked-out in glia, indicating that the protective actions of these receptors are largely glia-dependent. These data highlight a novel role of the endocannabinoid system at NMJs, where the CB1Rs on PSCs can control NMJ denervation and reinnervation following nerve injury. A better understanding of the functional mechanisms underlying CB1R role in NMJ repair may contribute to finding a new pharmacological treatment having a dual role in improvements of motor recovery and in pain-related relief.

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Diacylglycerol Signaling in Retinal Ganglion Cells

Chaplot,

Moceri,

Cabrera Gonzalez

et al. 2024

Methods in Molecular Biology

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Injury-induced activation of the endocannabinoid system promotes axon regeneration

Cited by 3 publications

References 48 publications

The role of cannabinoid CB1 receptors in the antinociceptive and reparative actions of mesenchymal stem cells in rats with peripheral neuropathic pain

The role of cannabinoid CB1 receptors in the antinociceptive and reparative actions of mesenchymal stem cells in rats with peripheral neuropathic pain

Cannabinoid type-1 (CB₁) receptors in glial cells promote neuromuscular junction repair following nerve injury

Diacylglycerol Signaling in Retinal Ganglion Cells

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Injury-induced activation of the endocannabinoid system promotes axon regeneration

Cited by 3 publications

References 48 publications

The role of cannabinoid CB1 receptors in the antinociceptive and reparative actions of mesenchymal stem cells in rats with peripheral neuropathic pain

The role of cannabinoid CB1 receptors in the antinociceptive and reparative actions of mesenchymal stem cells in rats with peripheral neuropathic pain

Cannabinoid type-1 (CB1) receptors in glial cells promote neuromuscular junction repair following nerve injury

Diacylglycerol Signaling in Retinal Ganglion Cells

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Cannabinoid type-1 (CB₁) receptors in glial cells promote neuromuscular junction repair following nerve injury