Biochemical effects of cannabinoids on oligodendrocytes: implications for schizophrenia

• Grant number: 18/03673-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2018
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Daniel Martins-de-Souza
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 19/03271-1 - Proteome modulation by cannabinoid drugs in human oligodendrocytes, BP.TT

Abstract

nd to discover possible therapeutic agents for this process. Studies indicate that the modulation of the endocannabinoid system in oligodendrocytes can affect important biological processes. Thus, the aim of this project will evaluate several pharmacological manipulations of the endocannabinoid system in human culture of oligodendrocytes (MO3.13), and in the differentiation process of these cells. These investigations may elucidate aspects of disorders with demyelinating processes, such as multiple sclerosis and schizophrenia. More specifically, studies have shown the involvement of the endocannabinoid system and oligodendrocytes in the pathophysiology of this schizophrenia. Thus, we will investigate the possible relationships between these two components. For this, MO3.13 culture cell will be treated with MK801 (NMDAr antagonist), which has been an in vitro model to study schizophrenia proposed by our group. We hope to identify the proteins and biochemical pathways affected by cannabinoids in immature and mature cells treated or not with MK801, as well as the influence on the differentiation process. Additionally, we will evaluate the effects of cannabinoids on cuprizone-induced demyelination in vtiro. For this, proteomic and molecular biology will be used. Finally, this study may contribute to the understanding of the role of the endocannabinoid system in oligodendrocytes and the possible implications for elucidating aspects of the pathophysiology of the demyelinating process and more specifically in the context of schizophrenia. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DIAS, THOMAZ LUSCHER; SCHUCH, VIVIANE; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA; MARTINS-DE-SOUZA, DANIEL; BRENTANI, HELENA PAULA; FRANCO, GLORIA REGINA; NAKAYA, HELDER IMOTO. Drug repositioning for psychiatric and neurological disorders through a network medicine approach. TRANSLATIONAL PSYCHIATRY, v. 10, n. 1, MAY 12 2020. (17/25588-1, 18/03673-0, 14/10068-4, 19/00098-7, 18/16748-8)

FALVELLA, ANA CAROLINE BRAMBILLA; SMITH, BRADLEY JOSEPH; SILVA-COSTA, LICIA C.; VALENCA, ALINE G. F.; CRUNFLI, FERNANDA; ZUARDI, ANTONIO W.; HALLAK, JAIME E.; CRIPPA, JOSE A.; ALMEIDA, VALERIA DE; MARTINS-DE-SOUZA, DANIEL. Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. FRONTIERS IN MOLECULAR NEUROSCIENCE, v. 14, MAY 28 2021. (18/03422-7, 08/09009-2, 17/18242-1, 19/00098-7, 17/25588-1, 19/22398-2, 18/10362-0, 18/03450-0, 18/03673-0)

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.; et al. Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 272, n. 7, p. 13-pg., 2022-05-27. (17/25588-1, 17/18242-1, 18/25818-0, 19/00098-7, 18/03673-0)

SEABRA, GABRIELA; DE ALMEIDA, VALERIA; REIS-DE-OLIVEIRA, GUILHERME; CRUNFLI, FERNANDA; LEAO MARCELO ANTUNES, ANDRE SARAIVA; MARTINS-DE-SOUZA, DANIEL. Ubiquitin-proteasome system, lipid metabolism and DNA damage repair are triggered by antipsychotic medication in human oligodendrocytes: implications in schizophrenia. SCIENTIFIC REPORTS, v. 10, n. 1, JUL 28 2020. (19/22398-2, 17/25588-1, 14/10068-4, 17/18242-1, 19/03271-1, 19/00098-7, 18/03673-0)

SEABRA, GABRIELA; FALVELLA, ANA CAROLINE B.; GUEST, PAUL C.; MARTINS-DE-SOUZA, DANIEL; DE ALMEIDA, VALERIA. Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains. PROTEOMICS, v. 18, n. 18, p. 16-pg., 2018-09-01. (18/10362-0, 17/18242-1, 18/03673-0)

ANTUNES, ANDRE S. L. M.; DE ALMEIDA, VALERIA; CRUNFLI, FERNANDA; CARREGARI, VICTOR C.; MARTINS-DE-SOUZA, DANIEL; GUEST, PC. Proteomics for Target Identification in Psychiatric and Neurodegenerative Disorders. REVIEWS ON NEW DRUG TARGETS IN AGE-RELATED DISORDERS, PT II, v. 1286, p. 14-pg., 2021-01-01. (19/22398-2, 17/25588-1, 17/18242-1, 19/05155-9, 18/03673-0)

SEABRA, GABRIELA; FALVELLA, ANA CAROLINE B.; GUEST, PAUL C.; MARTINS-DE-SOUZA, DANIEL; DE ALMEIDA, VALERIA. Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains. PROTEOMICS, v. 18, n. 18, SI, SEP 2018. (17/18242-1, 18/03673-0, 18/10362-0)

REIS-DE-OLIVEIRA, G.; ZUCCOLI, G. S.; FIORAMONTE, M.; SCHIMITT, A.; FALKAI, P.; ALMEIDA, V; MARTINS-DE-SOUZA, D.. Digging deeper in the proteome of different regions from schizophrenia brains. JOURNAL OF PROTEOMICS, v. 223, JUL 15 2020. (17/25588-1, 18/14666-4, 18/03673-0, 17/18242-1, 19/00098-7, 16/18715-4, 18/01410-1, 14/10068-4)

GOUVEA-JUNQUEIRA, DANIELLE; FALVELLA, ANA CAROLINE BRAMBILLA; ANTUNES, ANDRE SARAIVA LEAO MARCELO; SEABRA, GABRIELA; BRANDAO-TELES, CAROLINE; MARTINS-DE-SOUZA, DANIEL; CRUNFLI, FERNANDA. Novel Treatment Strategies Targeting Myelin and Oligodendrocyte Dysfunction in Schizophrenia. FRONTIERS IN PSYCHIATRY, v. 11, APR 30 2020. (17/25588-1, 17/25055-3, 18/03673-0, 19/22398-2, 18/10362-0, 18/25439-9)

RADAIC, ALLAN; MARTINS-DE-SOUZA, DANIEL. The state of the art of nanopsychiatry for schizophrenia diagnostics and treatment. Nanomedicine-Nanotechnology Biology and Medicine, v. 28, AUG 2020. (17/25588-1, 13/08711-3, 18/03673-0)