Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes

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de Almeida, Valeria ; Seabra, Gabriela ; Reis-de-Oliveira, Guilherme ; Zuccoli, Giuliana S. ; Rumin, Priscila ; Fioramonte, Mariana ; Smith, Bradley J. ; Zuardi, Antonio W. ; Hallak, Jaime E. C. ; Campos, Alline C. ; Crippa, Jose A. ; Martins-de-Souza, Daniel

• Document type: Journal article
• Source: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. 272, n. 7, p. 13-pg., 2022-05-27.

Abstract

Cannabinoid signaling, mainly via CB1 and CB2 receptors, plays an essential role in oligodendrocyte health and functions. However, the specific molecular signals associated with the activation or blockade of CB1 and CB2 receptors in this glial cell have yet to be elucidated. Mass spectrometry-based shotgun proteomics and in silico biology tools were used to determine which signaling pathways and molecular mechanisms are triggered in a human oligodendrocytic cell line (MO3.13) by several pharmacological stimuli: the phytocannabinoid cannabidiol (CBD); CB1 and CB2 agonists ACEA, HU308, and WIN55, 212-2; CB1 and CB2 antagonists AM251 and AM630; and endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The modulation of cannabinoid signaling in MO3.13 was found to affect pathways linked to cell proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Additionally, we found that carbohydrate and lipid metabolism, as well as mitochondrial function, were modulated by these compounds. Comparing the proteome changes and upstream regulators among treatments, the highest overlap was between the CB1 and CB2 antagonists, followed by overlaps between AEA and 2-AG. Our study opens new windows of opportunities, suggesting that cannabinoid signaling in oligodendrocytes might be relevant in the context of demyelinating and neurodegenerative diseases. Proteomics data are available at ProteomeXchange (PXD031923). (AU)

• FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/18242-1 - Biochemical pathways affected by cannabinoid drugs of human oligodendrocytes
• Grantee: Valéria de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/25818-0 - Role of cannabinoids in induced pluripotent stem cell-derived oligodendrocytes from schizophrenia patients
• Grantee: Valéria de Almeida
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 18/03673-0 - Biochemical effects of cannabinoids on oligodendrocytes: implications for schizophrenia
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Regular Research Grants