Oligodendrocytes: Potential of Discovering New Treatment Targets

Author(s)

Brandao-Teles, Caroline ^[1] ; de Almeida, Valeria ^[1] ; Cassoli, Juliana S. ^{[1, 2]} ; Martins-de-Souza, Daniel ^{[3, 1, 4]}

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, Campinas, SP - Brazil

^[2] Fac Palmas, Palmas - Brazil

^[3] UNICAMPs Neurobiol Ctr, Campinas, SP - Brazil

^[4] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 10, MAR 5 2019.
• Web of Science Citations: 1

Abstract

Schizophrenia is a psychiatric disorder that affects more than 21 million people worldwide. It is an incurable disorder and the primary means of managing symptoms is through administration of pharmacological treatments, which consist heavily of antipsychotics. First-generation antipsychotics have the properties of D-2 receptor antagonists. Second-generation antipsychotics are antagonists of both D-2 and 5HT(2) receptors. Recently, there has been increasing interest in the effects of antipsychotics beyond their neuronal targets and oligodendrocytes are one of the main candidates. Thus, our aim was to evaluate the molecular effects of typical and atypical drugs across the proteome of the human oligodendrocyte cell line, MO3.13. For this, we performed a mass spectrometry-based, bottom-up shotgun proteomic analysis to identify differences triggered by typical (chlorpromazine and haloperidol) and atypical (quetiapine and risperidone) antipsychotics. Proteins which showed changes in their expression levels were analyzed in silico using Ingenuity (R) Pathway Analysis, which implicated dysregulation of canonical pathways for each treatment. Our results shed light on the biochemical pathways involved in the mechanisms of action of these drugs, which may guide the identification of novel biomarkers and the development of new and improved treatments. (AU)

• 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 Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/14881-1 - Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia
• Grantee: Juliana Silva Cassoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/23049-0 - Employing human oligodendroglial cell cultures and glutamatergic dysfunction to understand the molecular basis of schizophrenia
• Grantee: Caroline Brandão Teles Rodrigues
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/18242-1 - Biochemical pathways affected by cannabinoid drugs of human oligodendrocytes
• Grantee: Valéria de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program