Influence of the endocannabinoid system on the energetic profile of neural cells during neurodevelopment: implications in Schizophrenia

• Grant number: 18/14666-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2018
• Effective date (End): October 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Giuliana da Silva Zuccoli
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Schizophrenia is a severe mental disorder, incapacitating and incurable that affects around 23 million people in the world. Among the hypotheses that try to explain the causes of Schizophrenia, the neurodevelopment hypothesis proposes that a combination of genetic and environmental disturbances since the development of the nervous system in utero are fundamental for the emergence of the disorder, that usually manifests itself in late adolescence/early adulthood. Several studies conducted on cerebral tissue from Schizophrenia patients collected postmortem point to dysfunctions in energy metabolism and mitochondrial processes. Recent results from our laboratory showed alterations in energy metabolism of Neural Stem Cells (NSC) and neurons derived from Induced Pluripotent Stem Cells (iPSC) from Schizophrenia patients, demonstrating that those alterations are observed during neurodevelopment. It is known that the modulation of the endocannabinoid system is important for key processes in neurodevelopment and can regulate neuronal bioenergetics. In this way, the present project proposes to derive cerebral organoids and neural cells from iPSC from Schizophrenia patients, recapitulating the processes that occur during neurodevelopment, and evaluate the situation of the energy and oxidative metabolism of those organoids and neural cells before and after treatment with cannabinoids. (AU)

Scientific publications

(8)

(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)

AKIYAMA, DANIEL YURI; ROCHA, MARINA CAMPOS; COSTA, JONAS HENRIQUE; TELES, CAROLINE BRANDAO; ZUCCOLI, GIULIANA DA SILVA; MALAVAZI, IRAN; FILL, TAICIA PACHECO. The Penicillium brasilianum Histone Deacetylase Clr3 Regulates Secondary Metabolite Production and Tolerance to Oxidative Stress. JOURNAL OF FUNGI, v. 8, n. 5, p. 18-pg., 2022-05-01. (19/06359-7, 18/13027-8, 17/19694-3, 18/14666-4, 18/00315-5, 17/25055-3, 16/07870-9)

NASCIMENTO, JULIANA MINARDI; GOUVEA-JUNQUEIRA, DANIELLE; ZUCCOLI, GIULIANA S.; GOUVEIA PEDROSA, CAROLINA DA SILVA; BRANDAO-TELES, CAROLINE; CRUNFLI, FERNANDA; ANTUNES, ANDRE S. L. M.; CASSOLI, JULIANA S.; KARMIRIAN, KARINA; SALERNO, JOSE ALEXANDRE; et al. Zika Virus Strains and Dengue Virus Induce Distinct Proteomic Changes in Neural Stem Cells and Neurospheres. Molecular Neurobiology, v. N/A, p. 15-pg., 2022-06-22. (18/25439-9, 14/21035-0, 17/25055-3, 18/14666-4, 19/00098-7, 20/10282-7, 17/25588-1)

ZUCCOLI, GIULIANA S.; GUEST, PAUL C.; MARTINS-DE-SOUZA, DANIEL; GUEST, PC. Effects on Glial Cell Glycolysis in Schizophrenia: An Advanced Aging Phenotype?. REVIEWS ON BIOMARKER STUDIES IN AGING AND ANTI-AGING RESEARCH, v. 1178, p. 14-pg., 2019-01-01. (17/25588-1, 18/14666-4)

ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; GARBES, BRUNA; FALKAI, PETER; SCHMITT, ANDREA; NAKAYA, I, HELDER; MARTINS-DE-SOUZA, DANIEL. Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, MAR 2021. (17/25588-1, 19/00098-7, 18/01410-1, 13/08216-2, 18/14666-4, 12/19278-6, 17/50137-3)

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)

JOSEPH SMITH, BRADLEY; BRANDAO-TELES, CAROLINE; ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; FIORAMONTE, MARIANA; SAIA-CEREDA, VERONICA M.; MARTINS-DE-SOUZA, DANIEL. Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia. JOURNAL OF PERSONALIZED MEDICINE, v. 12, n. 9, p. 15-pg., 2022-09-01. (14/10068-4, 16/07948-8, 17/25055-3, 15/23049-0, 18/01410-1, 18/14666-4, 19/05747-3, 16/07332-7, 13/08711-3, 19/00098-7, 17/25588-1)

NASCIMENTO, JULIANA MINARDI; SAIA-CEREDA, VERONICA M.; ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; CARREGARI, VICTOR CORASOLLA; SMITH, BRADLEY J.; REHEN, STEVENS K.; MARTINS-DE-SOUZA, DANIEL. Proteomic signatures of schizophrenia-sourced iPSC-derived neural cells and brain organoids are similar to patients' postmortem brains. CELL AND BIOSCIENCE, v. 12, n. 1, p. 16-pg., 2022-12-01. (17/25588-1, 19/25957-2, 14/21035-0, 19/05747-3, 18/14666-4, 19/00098-7, 18/01410-1, 16/07332-7)

ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; GARBES, BRUNA; FALKAI, PETER; SCHMITT, ANDREA; NAKAYA, I, HELDER; MARTINS-DE-SOUZA, DANIEL. Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 271, n. 8, p. 1579-1586, DEC 2021. (18/01410-1, 17/25588-1, 13/08216-2, 19/00098-7, 12/19278-6, 17/50137-3, 18/14666-4)