Witness stress promotes age and sex-dependent behavioral and neurofunctional alterations in the amygdaloid complex and dorsal hippocampus in mice

Author(s)

Avalo-Zuluaga, Julian Humberto ; Ramirez, Stephany Viatela ; Baptista-de-Souza, Daniela ; Canto-de-Souza, Lucas ; Rico, Javier Leonardo ; Nunes-de-Souza, Ricardo Luiz

• Document type: Journal article
• Source: Physiology & Behavior; v. 299, p. 13-pg., 2025-10-01.

Abstract

Humans are frequently exposed to stress, with social stress being a predominant factor, either directly experienced or observed. Chronic stress is linked to psychiatric disorders such as depression and anxiety and induces morpho-functional changes in brain areas like the amygdaloid complex and dorsal hippocampus, which influence emotional responses. This study examined the impact of witness social defeat stress (WSDS) on depression-like behaviors and neural activation in Swiss-Webster mice, considering variables like sex and life stage. Two experiments were conducted: Experiment 1 assessed the effects of WSDS in adulthood (58-60 postnatal days [PND]) on behaviors such as coat state, nest building, novel object exploration, and body weight gain, as well as neuronal activation in the amygdaloid complex and dorsal hippocampus. Experiment 2 evaluated the long-term effects of early WSDS exposure (21 PND) on these same parameters, reassessing mice at 58-62 PND. Results showed sex-dependent behavioral changes, including altered novel object interaction, coat and nest quality, and decreased Delta FosB Protein Expression in the amygdaloid complex and hippocampus, with age and sex influencing the stress response. WSDS in adulthood produced smaller behavioral changes, with some signs of resilience particularly in females, while early exposure to this type of stress led to more pronounced effects. This study highlights the complexity of stress responses, suggesting that the intensity and timing of stress, along with sex, play critical roles in shaping behavioral outcomes. (AU)

• FAPESP's process: 22/06260-3 - Functional lateralization assessment in the control of cardiovascular and behavioral responses to contextual fear conditioning by the medial prefrontal cortex in rats
• Grantee: Carlos Cesar Crestani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/04387-6 - Sex differences and oxytocinergic transmission impact on chronic pain in animal models and humans
• Grantee: Daniela Baptista de Souza
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 23/01341-8 - ASSESMENT OF THE ROLE OF THE AMYDALOID COMPLEX, DORSAL HIPPOCAMPUS AND THE INFLUENCE OF GENDER AND AGE ON RESPONSES RELATED TO DEPRESSION IN MICE SUBMITTED TO THE STRESS OF WITNESSING SOCIAL DEFEAT
• Grantee: Julian Humberto Avalo Zuluaga
• Support Opportunities: Scholarships in Brazil - Master