Evaluating the effects of clozapine on immune system cells

• Grant number: 18/01410-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): May 01, 2018
• Effective date (End): April 30, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Guilherme Reis-De-Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Schizophrenia is a heterogeneous and multifactorial disorder that affects around 21 million people worldwide. The disease is often characterized by the occurrence of positive, negative and cognitive symptoms. Several studies have shown that patients with schizophrenia present high concentrations of inflammatory molecules in the brain. These molecules could cross the blood brain barrier and change the homeostasis of the central nervous system. They can also interact with microglia, triggering an unsuitable inflammatory response in the brain, impairing the role of resident cells. Recent studies have revealed a decrease of microglia activation in animal models treated with clozapine. Although this antipsychotic is the main choice in refractory schizophrenia, clozapine can induce agranulocytosis as side effect, which may lead to death. Thus, here we are going to perform proteomic analyses of microglia cultures treated with the blood serum of schizophrenia patients, in addition to clozapine treatment, allowing the identification of key metabolic pathways to the disorder. The present project is also going to carry out proteomic analyses of clozapine-induced agranulocytosis in an ex vivo model, searching for potential therapeutic targets that could lead to the improvement of patients' health and quality of life. (AU)

Scientific publications

(5)

(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)

MARTINS-DE-SOUZA, DANIEL; GUEST, PAUL C.; REIS-DE-OLIVEIRA, GUILHERME; SCHMITT, ANDREA; FALKAI, PETER; TURCK, CHRISTOPH W.. An overview of the human brain myelin proteome and differences associated with schizophrenia. WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, v. 22, n. 4, JUL 2020. (19/00098-7, 18/01410-1, 17/25588-1)

FIORAMONTE, MARIANA; REIS-DE-OLIVEIRA, GUILHERME; BRANDAO-TELES, CAROLINE; MARTINS-DE-SOUZA, DANIEL. A glimpse on the architecture of hnRNP C1/C2 interaction network in cultured oligodendrocytes. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 12, DEC 2021. (18/01410-1, 16/18715-4, 17/25588-1, 19/00098-7, 17/25055-3)

REIS-DE-OLIVEIRA, G.; ZUCCOLI, G. S.; FIORAMONTE, M.; SCHIMITT, A.; FALKAI, P.; ALMEIDA, V; MARTINS-DE-SOUZA, D.. Digging deeper in the proteome of different regions from schizophrenia brains. JOURNAL OF PROTEOMICS, v. 223, JUL 15 2020. (17/25588-1, 18/14666-4, 18/03673-0, 17/18242-1, 19/00098-7, 16/18715-4, 18/01410-1, 14/10068-4)

ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; GARBES, BRUNA; FALKAI, PETER; SCHMITT, ANDREA; NAKAYA, I, HELDER; MARTINS-DE-SOUZA, DANIEL. Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 271, n. 8, p. 1579-1586, DEC 2021. (18/01410-1, 17/25588-1, 13/08216-2, 19/00098-7, 12/19278-6, 17/50137-3, 18/14666-4)

ZUCCOLI, GIULIANA S.; REIS-DE-OLIVEIRA, GUILHERME; GARBES, BRUNA; FALKAI, PETER; SCHMITT, ANDREA; NAKAYA, I, HELDER; MARTINS-DE-SOUZA, DANIEL. Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, MAR 2021. (17/25588-1, 19/00098-7, 18/01410-1, 13/08216-2, 18/14666-4, 12/19278-6, 17/50137-3)