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Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia

Grant number: 14/14881-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2014
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Biochemistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Daniel Martins-de-Souza
Grantee:Juliana Silva Cassoli
Home 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

Abstract

Schizophrenia is a chronic, severe and disabling psychiatric disorder that may affect up to 1% of population worldwide. The prevailing hypothesis for schizophrenia´s etiology is that disturbances in different levels of multiple risk genes, each one contributing a subtle effect, interact with environmental stimuli impacting brain development and function. Several methodologies, such as those employed in imaging, transcriptomics and proteomics studies, have been used in order to understand the molecular basis of schizophrenia. These studies have associated to the development and the establishment of this mental disorder dysfunctions in energy metabolism oligodendrocyte function. The aim of present project is to link these two components. We will characterize biochemical and morphological profiles using proteomic and microscopy techniques of oligodendrocyte precursor cells and myelinating oligodendrocytes subjected to overexpression and knock-down of glycolytic enzymes that such as aldolase C that we found differentially expressed in schizophrenia brains. With this, we hope to identify proteins and biochemical pathways affected by aldolase C modulation as well as its influence on morphology and function (myelination) of oligodendrocytes. Obtained data will be compared to previous findings in patients in order to observe whether the overexpression or knock-down of aldolase C is able to generate disturbances similar to those observed in schizophrenia. This study will contribute to understanding of the biochemical mechanisms involved in schizophrenia pathogenesis as well as the identification of key molecules that can be further studied, pointing out new therapeutic targets. (AU)

Articles published in Agência FAPESP about the scholarship:
Novel methodology increases resolution in oligodendrocyte proteomics 
Nova metodologia aumenta a resolução em análises de conjuntos de proteínas 
Research paves the way for a new treatment against schizophrenia 

Scientific publications (13)
(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. Web of Science Citations: 1.
CASSOLI, JULIANA S.; BRANDAO-TELES, CAROLINE; SANTANA, ALINE G.; SOUZA, GUSTAVO H. M. F.; MARTINS-DE-SOUZA, DANIEL. Ion Mobility-Enhanced Data-Independent Acquisitions Enable a Deep Proteomic Landscape of Oligodendrocytes. PROTEOMICS, v. 17, n. 21 NOV 2017. Web of Science Citations: 3.
SAIA-CEREDA, VERONICA M.; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL; NASCIMENTO, JULIANA M. Psychiatric disorders biochemical pathways unraveled by human brain proteomics. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 267, n. 1, p. 3-17, FEB 2017. Web of Science Citations: 6.
GARCEZ, PATRICIA P.; NASCIMENTO, JULIANA MINARDI; DE VASCONCELOS, JANAINA MOTA; DA COSTA, RODRIGO MADEIRO; DELVECCHIO, RODRIGO; TRINDADE, PABLO; LOIOLA, ERICK CORREIA; HIGA, LUIZA M.; CASSOLI, JULIANA S.; VITORIA, GABRIELA; SEQUEIRA, PATRICIA C.; SOCHACKI, JAROSLAW; AGUIAR, RENATO S.; FUZII, HELLEN THAIS; BISPO DE FILIPPIS, ANA M.; GONCALVES VIANEZ JUNIOR, JOAO LIDIO DA SILVA; TANURI, AMILCAR; MARTINS-DE-SOUZA, DANIEL; REHEN, STEVENS K. Zika virus disrupts molecular fingerprinting of human neurospheres. SCIENTIFIC REPORTS, v. 7, JAN 23 2017. Web of Science Citations: 23.
TAVARES, RAPHAEL; WAJNBERG, GABRIEL; SCHERER, NICOLE DE MIRANDA; PAULETTI, BIANCA ALVES; CASSOLI, JULIANA S.; FERREIRA, CARLOS GIL; PAES LEME, ADRIANA FRANCO; DE ARAUJO-SOUZA, PATRICIA SAVIO; MARTINS-DE-SOUZA, DANIEL; PASSETTI, FABIO. Unveiling alterative splice diversity from human oligodendrocyte proteome data. JOURNAL OF PROTEOMICS, v. 151, n. SI, p. 293-301, JAN 16 2017. Web of Science Citations: 1.
SCHMITT, ANDREA; MARTINS-DE-SOUZA, DANIEL; AKBARIAN, SCHAHRAM; CASSOLI, JULIANA S.; EHRENREICH, HANNELORE; FISCHER, ANDRE; FONTEH, ALFRED; GATTAZ, WAGNER F.; GAWLIK, MICHAEL; GERLACH, MANFRED; GRUNBLATT, EDNA; HALENE, TOBIAS; HASAN, ALKOMIET; HASHIMOTO, KENIJ; KIM, YONG-KU; KIRCHNER, SOPHIE-KATHRIN; KORNHUBER, JOHANNES; KRAUS, THEO F. J.; MALCHOW, BEREND; NASCIMENTO, JULIANA M.; ROSSNER, MORITZ; SCHWARZ, MARKUS; STEINER, JOHANN; TALIB, LEDA; THIBAUT, FLORENCE; RIEDERER, PETER; FALKAI, PETER; FORCE, MEMBERS WFSBP TASK. Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms. WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, v. 18, n. 5, p. 330-356, 2017. Web of Science Citations: 4.
NASCIMENTO, JULIANA M.; GARCIA, SHEILA; SAIA-CEREDA, VERONICA M.; SANTANA, ALINE G.; BRANDAO-TELES, CAROLINE; ZUCCOLI, GIULIANA S.; JUNQUEIRA, DANIELLE G.; REIS-DE-OLIVEIRA, GUILHERME; BALDASSO, PAULO A.; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL. Proteomics and molecular tools for unveiling missing links in the biochemical understanding of schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 12, SI, p. 1148-1158, DEC 2016. Web of Science Citations: 3.
SAIA-CEREDA, VERONICA M.; CASSOLI, JULIANA S.; SCHMITT, ANDREA; FALKAI, PETER; MARTINS-DE-SOUZA, DANIEL. Differential proteome and phosphoproteome may impact cell signaling in the corpus callosum of schizophrenia patients. SCHIZOPHRENIA RESEARCH, v. 177, n. 1-3, p. 70-77, NOV 2016. Web of Science Citations: 7.
CASSOLI, JULIANA S.; GUEST, PAUL C.; SANTANA, ALINE G.; MARTINS-DE-SOUZA, DANIEL. Employing proteomics to unravel the molecular effects of antipsychotics and their role in schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 4, SI, p. 442-455, APR 2016. Web of Science Citations: 4.
CASSOLI, JULIANA S.; IWATA, KEIKO; STEINER, JOHANN; GUEST, PAUL C.; TURCK, CHRISTOPH W.; NASCIMENTO, JULIANA M.; MARTINS-DE-SOUZA, DANIEL. Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 10, MAR 3 2016. Web of Science Citations: 13.
MARTINS-DE-SOUZA, DANIEL; CASSOLI, JULIANA S.; NASCIMENTO, JULIANA M.; HENSLEY, KENNETH; GUEST, PAUL C.; PINZON-VELASCO, ANDRES M.; TURCK, CHRISTOPH W. The protein interactome of collapsin response mediator protein-2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue. PROTEOMICS CLINICAL APPLICATIONS, v. 9, n. 9-10, SI, p. 817-831, OCT 2015. Web of Science Citations: 13.
SAIA-CEREDA, VERONICA M.; CASSOLI, JULIANA S.; SCHMITT, ANDREA; FALKAI, PETER; NASCIMENTO, JULIANA M.; MARTINS-DE-SOUZA, DANIEL. Proteomics of the corpus callosum unravel pivotal players in the dysfunction of cell signaling, structure, and myelination in schizophrenia brains. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 265, n. 7, p. 601-612, OCT 2015. Web of Science Citations: 27.
CASSOLI, JULIANA SILVA; GUEST, PAUL C.; MALCHOW, BEREND; SCHMITT, ANDREA; FALKAI, PETER; MARTINS-DE-SOUZA, DANIEL. Disturbed macro-connectivity in schizophrenia linked to oligodendrocyte dysfunction: from structural findings to molecules. NPJ SCHIZOPHRENIA, v. 1, 2015. Web of Science Citations: 18.

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