Biochemical pathways affected by cannabinoid drugs of human oligodendrocytes

• Grant number: 17/18242-1
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2018
• Effective date (End): February 28, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Valéria de Almeida
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics, AP.JP
• Associated scholarship(s): 18/25818-0 - Role of cannabinoids in induced pluripotent stem cell-derived oligodendrocytes from schizophrenia patients, BE.EP.PD

Abstract

Growing interest in the role of oligodendrocytes in psychiatric disorders has been noted. The main function of oligodendrocytes is related to neuronal myelination, and damage in the myelination affects the action potentials and consequently the connectivity between different brain regions. In this regard, studies have investigated the effect of pharmacological tools on mature oligodendrocytes and their precursor cells to understand the pathological processes of demyelination, and 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. 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.

Scientific publications

(6)

(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)

BRANDAO-TELES, CAROLINE; DE ALMEIDA, VALERIA; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL. Oligodendrocytes: Potential of Discovering New Treatment Targets. FRONTIERS IN PHARMACOLOGY, v. 10, MAR 5 2019. (17/25588-1, 14/14881-1, 15/23049-0, 17/18242-1, 14/10068-4)

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)

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)

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)

DE ALMEIDA, VALERIA; ALEXANDRINO, GUILHERME L.; AQUINO, ADRIANO; GOMES, ALEXANDRE F.; MURGU, MICHAEL; DOBROWOLNY, HENRIK; GUEST, PAUL C.; STEINER, JOHANN; MARTINS-DE-SOUZA, DANIEL. Changes in the blood plasma lipidome associated with effective or poor response to atypical antipsychotic treatments in schizophrenia patients. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 101, JUL 13 2020. (17/25588-1, 15/08201-0, 14/10068-4, 17/18242-1, 15/09159-8, 19/00098-7)