Selective blockade of cannabinoid receptors influences motoneuron survival and glial responses after neonatal axotomy

Author(s)

Perez, Matheus ; Spejo, Aline Barroso ; Chiarotto, Gabriela Bortolanca ; Guimaraes, Francisco Silveira ; de Oliveira, Alexandre Leite Rodrigues ; Cartarozzi, Luciana Politti

• Document type: Journal article
• Source: Neuroscience; v. 565, p. 12-pg., 2024-12-10.

Abstract

Sciatic nerve crush in neonatal rats leads to an extensive death of motor and sensory neurons, serving as a platform to develop new neuroprotective approaches. The endocannabinoid system plays important neuromodulatory roles and has been involved in neurodevelopment and neuroprotection. The present work investigated the role of the cannabinoid receptors CB1 and CB2 in the neuroprotective response after neonatal axotomy. CB1 and CB2 antagonists (AM251 and AM630, respectively) were used after sciatic nerve crush in 2-day-old Wistar rats. Five days after lesion and treatment, the rats were perfused, and the spinal cords and dorsal root ganglia (DRG) were obtained and processed to investigate neuronal survival and immunohistochemistry changes, or RT-qPCR analysis. Motoneuron survival analysis showed that blocking CB2 alone or in combination with CB1 was neuroprotective. This effect was associated with a decrease in astrogliosis and microglial reaction. Interestingly, Cnr1 (CB1) and Bdnf gene transcripts were downregulated in the spinal cords of the antagonist-treated groups. Despite no intergroup difference regarding neuronal survival in the DRG, the simultaneous blockade of CB1 and CB2 receptors led to an increased expression of both Cnr1 and Cnr2, combined with Gdnf upregulation. The results indicate that the selective antagonism of cannabinoid receptors facilitates neuroprotection and decreases glial reactivity, suggesting new potential treatment approaches. (AU)

• FAPESP's process: 22/06609-6 - Glutamatergic signaling after rachimedullary trauma: role of glial cells in the inflammatory response and excitotoxicity
• Grantee: Luciana Politti Cartarozzi
• Support Opportunities: Generation Project Research Grant
• FAPESP's process: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants