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

• Grant number: 14/14881-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2014
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Juliana Silva Cassoli
• 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

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)

Scientific publications

(17)

(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)

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. (14/14881-1, 13/08711-3)

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. (14/10068-4, 14/14881-1, 13/25702-8, 13/08711-3)

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. (14/10068-4, 14/14881-1, 13/08711-3)

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. (14/21035-0, 14/10068-4, 14/14881-1, 13/08711-3)

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. (14/10068-4, 14/14881-1, 13/08711-3)

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. (14/21035-0, 14/14881-1, 13/08711-3)

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.; et al. Proteomics and molecular tools for unveiling missing links in the biochemical understanding of schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 12, p. 11-pg., 2016-12-01. (15/23049-0, 14/21035-0, 16/04912-2, 13/08711-3, 14/14881-1)

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, p. 9-pg., 2017-01-16. (14/10068-4, 10/19278-0, 09/54067-3, 14/14881-1, 13/08711-3)

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.; et al. 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. (14/14881-1, 15/23049-0, 16/04912-2, 13/08711-3, 14/21035-0)

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. (14/14881-1, 09/54067-3, 13/08711-3, 14/10068-4, 10/19278-0)

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. (15/23049-0, 14/14881-1, 13/08711-3, 14/10068-4)

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; et al. Zika virus disrupts molecular fingerprinting of human neurospheres. SCIENTIFIC REPORTS, v. 7, JAN 23 2017. (14/21035-0, 14/10068-4, 13/08711-3, 14/14881-1)

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)

SCHMITT, ANDREA; MARTINS-DE-SOUZA, DANIEL; AKBARIAN, SCHAHRAM; CASSOLI, JULIANA S.; EHRENREICH, HANNELORE; FISCHER, ANDRE; FONTEH, ALFRED; GATTAZ, WAGNER F.; GAWLIK, MICHAEL; GERLACH, MANFRED; et al. 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. (14/21035-0, 14/10068-4, 14/14881-1, 13/08711-3)

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. (14/21035-0, 14/10068-4, 14/14881-1, 13/08711-3)

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, p. 15-pg., 2015-10-01. (13/08711-3, 13/25702-8, 14/14881-1, 14/10068-4)

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, p. 14-pg., 2016-04-01. (13/08711-3, 14/14881-1)