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Biochemical Pathways Triggered by Antipsychotics in Human Oligodendrocytes: Potential of Discovering New Treatment Targets

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 D2 receptor antagonists. Second-generation antipsychotic are antagonists of both D2 and 5HT2 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® 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.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Caroline Teles

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD008892 | Pride | 2019-11-12

REPOSITORIES: Pride

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Biochemical Pathways Triggered by Antipsychotics in Human [corrected] Oligodendrocytes: Potential of Discovering New Treatment Targets.

Brandão-Teles Caroline C de Almeida Valéria V Cassoli Juliana S JS Martins-de-Souza Daniel D

Frontiers in pharmacology 20190305

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 D2 receptor antagonists. Second-generation antipsychotics are antagonists of both D2 and 5HT2 receptors. Recently, there has been increasing interest i ...[more]

PMID: 30890939

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			Action	DRS
	Chlorp.rar	Other
	ChlorxHCl_peptide.csv	Csv
	ChlorxHCl_proteins.csv	Csv
	Halop.rar	Other
	HalopxHCl_peptide.csv	Csv