NEUROIMMUNE MECHANISMS UNDERLYING BEHAVIOURAL CHANGES FOLLOWING EARLY LIFE STRESS

• Grant number: 24/13469-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: December 29, 2024
• End date: December 28, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Hélio Zangrossi Júnior
• Grantee: Arthur Rocha Gomes
• Supervisor: Valentina Mosienko
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Bristol, England
• Associated to the scholarship: 21/08968-0 - Behavioral and neuroinflammatory effects caused by a simulated poverty model in mice: implications for panic disorder, BP.PD

Abstract

Anxiety disorders are one of the most common mental health illnesses affecting about 4% of the global population. Anxiety is a chronic and disabling condition characterized among others by excessive worry, fears related to social and performance situations and panic attacks. Experiencing adversity early in life increases the risk of developing anxiety later in adulthood on average by 3.5 times. However, molecular and cellular mechanisms driving susceptibility to anxiety disorders following early life stress is not fully understood. In this study, we will investigate neuroimmune mechanisms underlying maladaptive behavioral responses following early life stress, using the limited bedding and nesting (LBN) mouse model to mimic adverse conditions. Restraint stress in adult mice will be used to further probe susceptibility of LBN model to evoke anxiety-like behaviors in a two-hit approach, that will be quantified in the elevated plus maze, open field, and lightdark box tests. Next, we will measure activation of microglia and astrocytes in brain areas driving emotional responses to stress including amygdala, hippocampus and prefrontal cortex using an innovative pipeline for morphological assessment developed in the host laboratory. In the final phase of this project, we will test if behavioral responses to stress in LBN model improve following microglia depletion performed prior the exposure to the second stressor. The current study will expand our knowledge on neuroimmune mechanisms following early life adversity and driving anxiety and will be the first step towards exploring potential novel targets effective in improving mental health. Additionally, through this internship, we will acquire knowledge about the development of advanced pipelines for cell analysis, the effects of neonatal stressors on anxiety behaviors, two-hit protocols, and the use of a microglia-depleting drug in these models.