Investigation of neuroinflammation and blood-brain barrier dysfunction biomarkers in the post-mortem prefrontal cortex of individuals with a clinical history of Major Depressive Disorder

• Grant number: 24/15871-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Camila Nascimento Mantelli
• Grantee: Ariany de Fatima Kanashiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/13345-2 - The hypothalamus in major depressive disorder: a multiomics single-nucleus study, AP.JP

Abstract

Major Depressive Disorder (MDD) is characterized as a debilitating disorder with a rising prevalence in society, making it a significant public mental health issue. Its neurobiological bases are not yet fully elucidated due to the complex nature of its etiopathogenesis. Among the neurobiological hypothesis of depression is the inflammatory hypothesis, based on the increase in peripheral inflammatory factors consistently observed in MDD patients. Additionally, some studies have also demonstrated the presence of neuroinflammation in brain areas implicated in the pathophysiology of this disorder. However, the relationship between peripheral inflammation and neuroinflammation is not yet fully understood. Interest has emerged in the possible dysfunction of the blood-brain barrier (BBB) as an important regulatory mechanism of systemic inflammation and neuroinflammation in MDD. The BBB is primarily composed of endothelial cells, tight and adherens junction proteins, pericytes, and astrocytic end-feet, and functions as a crucial interface between brain tissue and blood. Recent studies have shown the presence of astrocyte marker proteins in the peripheral blood of MDD patients, indicating BBB dysfunction. However, few studies have assessed changes in structural BBB proteins in the brain of individuals with MDD. Therefore, we aim to evaluate the relationship between neuroinflammation and BBB integrity by investigating levels of pro-inflammatory cytokines IL-6 and TNF-¿, and tight junction proteins claudin-5 (cldn-5) and occludin in the post-mortem dorsolateral prefrontal cortex of MDD patients. Additionally, we will use previously published single-cell data generated from the same brain region in MDD individuals to explore the origins of these potential changes in our targets, such as identifying which cell types are responsible for their production and which gene networks may be altered.