Characterizing the intracellular proteome associated with combined venlafaxine and atypical antipsychotic treatment in a human immature oligodendrocyte cell line

• Grant number: 24/00735-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Caio Henrique de Souza Ferreira Berdeville
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study, AP.TEM

Abstract

Schizophrenia is characterized by the onset of positive (delusions and hallucinations), negative (such as anhedonia), and cognitive symptoms and affects nearly 200 million people worldwide. The atypical antipsychotics used to treat this disease work by blocking dopamine D2 receptors and antagonizing 5-HT2A receptors. Nearly 26% of patients with a first episode of psychosis present with depressive symptoms in the post-acute phase, modifying both clinical and psychosocial presentations. For the management of this condition, the overlap between both antipsychotics and antidepressants is required as a pharmacological tool, which is also needed in cases of psychotic depression or treatment-resistant depression. Antidepressants act by increasing the levels of monoamines at the synaptic cleft, with the majority of first-line medications selectively inhibiting the reuptake of serotonin; however, venlafaxine also inhibits the reuptake of noradrenaline by interacting with both serotonin and noradrenaline transporters, SERT and NET, respectively, and with the 5-HT1A and alpha-2 autoreceptors. Oligodendrocytes are fundamental cells of the nervous tissue, with venlafaxine enhancing the expression of myelin markers in murine models, while the use of antipsychotics, in human cells, changes processes related to the metabolism of protein and nucleic acid, and signal transduction. At present, there is a gap in the literature regarding the molecular phenomena underlying the augmentation of venlafaxine exposure with atypical antipsychotics, especially considering that both classes act by modulating serotoninergic pathways but also regulating noradrenergic and dopaminergic pathways, respectively. Therefore, the aim of this project is to characterize the intracellular proteome associated with the combined venlafaxine and atypical antipsychotic treatment in an immature oligodendrocyte cell line (MO3.13).

Scientific publications

(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)

BERDEVILLE, CAIO HENRIQUE DE SOUZA FERREIRA; SILVA-AMARAL, DANYELLE; DALGALARRONDO, PAULO; BANZATO, CLAUDIO E. M.; MARTINS-DE-SOUZA, DANIEL. A scoping review of protein biomarkers for schizophrenia: State of progress, underlying biology, and methodological considerations. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 168, p. 18-pg., 2025-01-01. (23/01211-7, 24/00735-5, 17/25588-1, 22/16373-0)