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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Novel Treatment Strategies Targeting Myelin and Oligodendrocyte Dysfunction in Schizophrenia

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Gouvea-Junqueira, Danielle [1] ; Falvella, Ana Caroline Brambilla [1] ; Antunes, Andre Saraiva Leao Marcelo [1] ; Seabra, Gabriela [1] ; Brandao-Teles, Caroline [1] ; Martins-de-Souza, Daniel [2, 3, 1, 4] ; Crunfli, Fernanda [1]
Total Authors: 7
[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, Campinas - Brazil
[2] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria, Sao Paulo - Brazil
[3] Univ Estadual Campinas, Expt Med Res Cluster, Campinas - Brazil
[4] DOr Inst Res & Educ IDOR, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Review article
Source: FRONTIERS IN PSYCHIATRY; v. 11, APR 30 2020.
Web of Science Citations: 1

Oligodendrocytes are the glial cells responsible for the formation of the myelin sheath around axons. During neurodevelopment, oligodendrocytes undergo maturation and differentiation, and later remyelination in adulthood. Abnormalities in these processes have been associated with behavioral and cognitive dysfunctions and the development of various mental illnesses like schizophrenia. Several studies have implicated oligodendrocyte dysfunction and myelin abnormalities in the disorder, together with altered expression of myelin-related genes such as Olig2, CNP, and NRG1. However, the molecular mechanisms subjacent of these alterations remain elusive. Schizophrenia is a severe, chronic psychiatric disorder affecting more than 23 million individuals worldwide and its symptoms usually appear at the beginning of adulthood. Currently, the major therapeutic strategy for schizophrenia relies on the use of antipsychotics. Despite their widespread use, the effects of antipsychotics on glial cells, especially oligodendrocytes, remain unclear. Thus, in this review we highlight the current knowledge regarding oligodendrocyte dysfunction in schizophrenia, compiling data from (epi)genetic studies and up-to-date models to investigate the role of oligodendrocytes in the disorder. In addition, we examined potential targets currently investigated for the improvement of schizophrenia symptoms. Research in this area has been investigating potential beneficial compounds, including the D-amino acids D-aspartate and D-serine, that act as NMDA receptor agonists, modulating the glutamatergic signaling; the antioxidant N-acetylcysteine, a precursor in the synthesis of glutathione, protecting against the redox imbalance; as well as lithium, an inhibitor of glycogen synthase kinase 3 beta (GSK3 beta) signaling, contributing to oligodendrocyte survival and functioning. In conclusion, there is strong evidence linking oligodendrocyte dysfunction to the development of schizophrenia. Hence, a better understanding of oligodendrocyte differentiation, as well as the effects of antipsychotic medication in these cells, could have potential implications for understanding the development of schizophrenia and finding new targets for drug development. (AU)

FAPESP's process: 19/22398-2 - The role of cholesterol synthesis in the mode of action of clozapine in schizophrenia models
Grantee:Fernanda Crunfli
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
Grantee:Daniel Martins-de-Souza
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/25439-9 - Proteomic profile of neural stem cells and neurospheres infected with Zika virus and Dengue virus
Grantee:Danielle Gouvêa Junqueira
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/10362-0 - Evaluation of the effect of antipsychotics and the cannabidiol in an oligodendrocytes culture treated with cuprizone: implications for myelination
Grantee:Ana Caroline Brambilla Falvella
Support type: Scholarships in Brazil - Master
FAPESP's process: 17/25055-3 - The role of hnRNPs in oligodendrocytes and their implications on schizophrenia
Grantee:Caroline Brandão Teles Rodrigues
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/03673-0 - Biochemical effects of cannabinoids on oligodendrocytes: implications for schizophrenia
Grantee:Daniel Martins-de-Souza
Support type: Regular Research Grants