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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
Número total de Autores: 12
Tipo de documento: Artigo Científico
Fonte: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. 272, n. 7, p. 13-pg., 2022-05-27.
Resumo

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)

Processo FAPESP: 17/25588-1 - Da compreensão básica a biomarcadores clínicos para a esquizofrenia: um estudo multidisciplinar centrado na neuroproteômica
Beneficiário:Daniel Martins-de-Souza
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/18242-1 - Vias bioquímicas moduladas por drogas canabinóides em oligodendrócitos humanos
Beneficiário:Valéria de Almeida
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 18/25818-0 - Papel dos canabinóides em oligodendrócitos gerados a partir de células tronco pluripotentes derivadas de pacientes com esquizofrenia
Beneficiário:Valéria de Almeida
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
Processo FAPESP: 19/00098-7 - EMU concedido no processo 2017/25588-1: cromatógrafo Acquity UPLC I-Class
Beneficiário:Daniel Martins-de-Souza
Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 18/03673-0 - Efeitos bioquímicos de canabinóides em oligodendrócitos: implicações para a esquizofrenia
Beneficiário:Daniel Martins-de-Souza
Modalidade de apoio: Auxílio à Pesquisa - Regular