Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13

Author(s)

Falvella, Ana Caroline Brambilla ^[1] ; Smith, Bradley Joseph ^[1] ; Silva-Costa, Licia C. ^[1] ; Valenca, Aline G. F. ^[1] ; Crunfli, Fernanda ^[1] ; Zuardi, Antonio W. ^[2] ; Hallak, Jaime E. ^[2] ; Crippa, Jose A. ^[2] ; Almeida, Valeria de ^[1] ; Martins-de-Souza, Daniel ^{[3, 4, 1, 5]}

Affiliation

^[1] Univ Campinas UNICAMP, Lab Neuroprote, Dept Biochem & Tissue Biol, Inst Biol, Campinas - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Neurosci & Behav, Ribeirao Preto - Brazil

^[3] DOr Inst Res & Educ IDOR, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Expt Med Res Cluster EMRC, Campinas - Brazil

^[5] Conselho Nacl Dev Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria INBION, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN MOLECULAR NEUROSCIENCE; v. 14, MAY 28 2021.
• Web of Science Citations: 0

Abstract

Cannabidiol, a compound of Cannabis sativa, has been proposed as an alternative treatment of schizophrenia. Preclinical and clinical data have suggested that cannabidiol shares more similarity with atypical antipsychotics than typical, both of which are customarily used to manage schizophrenia symptoms. While oligodendrocytes are known to be relevant targets of antipsychotics, the biochemical knowledge in this regard is still limited. Here we evaluated the molecular pathways modulated by cannabidiol compared to the antipsychotics clozapine (atypical) and haloperidol (typical), additionally evaluating the effects of benztropine, a muscarinic receptor antagonist that displays a protective effect in oligodendrocytes and myelination. For this purpose, we employed nano-chromatography coupled with mass spectrometry to investigate the proteomic response to these drugs both in healthy oligodendrocytic cells and in a cuprizone-based toxicity model, using the human oligodendrocyte precursor cell line MO3.13. Cannabidiol shares similarities of biochemical pathways with clozapine and benztropine, in agreement with other studies that indicated an atypical antipsychotic profile. All drugs tested affected metabolic and gene expression pathways and cannabidiol, benztropine, and clozapine modulated cell proliferation and apoptosis when administered after cuprizone-induced toxicity. These general pathways are associated with cuprizone-induced cytotoxicity in MO3.13 cells, indicating a possible proteomic approach when acting against the toxic effects of cuprizone. In conclusion, although modeling oligodendrocytic cytotoxicity with cuprizone does not represent the entirety of the pathophysiology of oligodendrocyte impairments, these results provide insight into the mechanisms associated with the effects of cannabidiol and antipsychotics against cuprizone toxicity, offering new directions of study for myelin-related processes and deficits. (AU)

• FAPESP's process: 18/03422-7 - Identification of blood-based biomarkers for late-life depression through proteomics
• Grantee: Licia Carla da Silva Costa
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 08/09009-2 - Crack/cocaine chronic use: dopamine transporters availability, genetic factors, and executive functioning
• Grantee: Acioly Luiz Tavares de Lacerda
• Support Opportunities: Regular Research 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: 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: 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: 19/22398-2 - The role of cholesterol synthesis in the mode of action of clozapine in schizophrenia models
• Grantee: Fernanda Crunfli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/10362-0 - Evaluation of the effect of antipsychotics and the cannabidiol in an oligodendrocytes culture treated with cuprizone: implications for myelination
• Grantee: Ana Caroline Brambilla Falvella
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/03450-0 - Study of Metabolic Syndrome on clozapine treated adipocytes
• Grantee: Aline Gazzola Fragnani Valença
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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