Evaluation of the relationship of astrocytes and neurons in response to inflammation in major depressive disorder

• Grant number: 24/12994-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Julia Louise Moreira Nacif
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Major depressive disorder (MDD) is a complex and multifactorial disease, which involves genetic, environmental and social factors, and affects approximately 280 million people worldwide, being one of the most disabling diseases in the world. Currently, treatment for the disease consists of drugs that modulate monoaminergic systems. However, approximately 30% of patients are refractory, which suggests that other mechanisms of action are involved in the pathology of the disease and need to be considered as therapeutic targets. Evidence indicates that inflammation is associated with the establishment and progression of depression, and glial cells are key components of this process. Astrocytes participate in the inflammatory process of the central nervous system, responding to external and internal stimuli, and can play a neurotoxic or neuroprotective role, depending on how they are activated. This activation has been associated with the development of several neurobiological diseases, such as depression, and therefore needs to be further explored. The present project proposes to establish an inflammation model for the study of depression in vitro, and to evaluate the relationship between astrocytes-neurons in this context, using human induced pluripotent stem cells derived from somatic cells collected from neurotypical subjects and patients with refractory depression and in remission. Differentiated astrocytes and neurons will be cultured in indirect transwell coculture and characterized by proteomics after exposure to IL-1² and TNF-±, as the inflammatory insult. Functional analyzes in astrocytes and neurons will be guided by the proteomic differences to be observed. Based on the results obtained, it is expected to expand knowledge about the pathophysiology of depression and resistance mechanisms, which can contribute to the discovery of potential biomarkers and new therapeutic targets for depression.