Molecular alterations in glutamatergic neurons exposed to clozapine-treated adipocytes conditioned medium.

• Grant number: 24/09395-2
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: September 30, 2024
• End date: March 29, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Júlia de Moraes Crisostomo
• Supervisor: Maria Carolina Nasser Marchetto
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 23/02834-8 - Molecular alterations in astrocytes exposed to adipocyte-conditioned medium treated with clozapine, BP.MS

Abstract

Antipsychotics are a group of drugs used mainly to treat psychotic disorders like schizophrenia. Generally, they act as dopamine receptor agonists but also can affect adrenergic, serotonergic, cholinergic, and histamine receptors, which promote the management of a range of symptoms. Clozapine is considered one of the most effective antipsychotics. However, despite its benefits, clozapine could cause undesirable side effects. It may lead to metabolic syndrome, which usually includes dysfunction in adipose tissue. Recent results of our work indicate that the clozapine-treated white adipocytes conditioned medium demonstrated the ability to modulate proteins associated with the glutamatergic pathways in astrocytes. The glutamatergic pathways act as a connection between astrocytes and neurons. Through this association, glutamate is first released by glutamatergic neurons and transported into astrocytes by EAATs (excitatory amino acid transporters), where it is converted into glycine. Astrocytes then release glycine into the extracellular space where it can be reabsorbed by neurons and converted back into glutamate, completing the cycle. Considering the role of the glutamatergic neurons and our recent findings, this project aims to investigate glutamatergic neurons response to clozapine-treated adipocyte conditioned media and analyze the correlation between astrocytes and glutamatergic neurons response associated with the endocrine role of adipocytes in this context.