Molecular alterations in astrocytes exposed to adipocyte-conditioned medium treated with clozapine

• Grant number: 23/02834-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2023
• End date: September 01, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Júlia de Moraes Crisostomo
• 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
• Associated scholarship(s): 24/09395-2 - Molecular alterations in glutamatergic neurons exposed to clozapine-treated adipocytes conditioned medium., BE.EP.MS

Abstract

Schizophrenia is a psychiatric disorder that affects approximately 20 million people worldwide and currently, no cure has been discovered. The disorder is characterized by a variety of symptoms, including positive symptoms (hallucinations and delusions); negative symptoms (social withdrawal, depression, and lack of motivation); and cognitive symptoms (difficulty with concentration, deficits in executive functions and long-term memory failure). The typical approach for treating schizophrenia involves the use of antipsychotic drugs, which are designed to reduce the symptoms associated with the disorder. Clozapine is an antipsychotic medication that is particularly effective in managing positive symptoms and treating patients who are unresponsive to other treatments. Despite its many benefits, clozapine can also cause significant side effects. In some patients, it can induce the development of metabolic syndrome, which is characterized by rapid weight gain, diabetes, and cardiovascular problems, usually caused by dysfunctions in adipose tissue. Adipocytes have an important endocrine function, secreting metabolites that modulate several physiological reactions. Metabolites secreted by adipocytes have the ability to influence several physiological reactions. For example, high levels of leptin can stimulate astrocytes to produce pro-inflammatory cytokines. Astrocytes play a critical role as a line of defense in the central nervous system, actively involved in regulating cellular homeostasis and facilitating tissue repair. Considering the importance of antipsychotics in the context of schizophrenia, the association of adipocytes with the metabolic syndrome and the participation of astrocytes in brain homeostasis, it is relevant to evaluate the molecular alterations in astrocytes induced by exposure to molecular factors secreted by adipocytes treated with clozapine, aiming to better understand the role of both cells during the treatment.