Early life stress (ELS) increases vulnerability to psychiatric disorders. However, the mechanisms behind this increase remain unknown. Using maternal separation with early weaning (MSEW) to model ELS in mice, a study in Behavioural Brain Research evaluated emotional behavior, intestinal permeability and hippocampal neuroinflammatory markers in both sexes. Behavioral testing in 2-month-old mice revealed that MSEW induced persistent anxiety- and depression-like behaviors, with females displaying stronger anxiety responses compared to males. MSEW also produced anhedonia, elevated gut permeability and a correlation between gut barrier dysfunction and emotional impairments. At the molecular level, MSEW increased hippocampal NF-κB expression while reducing TNF-α, particularly in males, and elevated brain-derived neurotrophic factor without altering adult neurogenesis. These results show that MSEW induces long-term alterations in both gut and brain, supporting a gut–brain axis role in mood dysregulation. The study highlights intestinal permeability as a potential biomarker and therapeutic target for stress-related psychiatric conditions, showing the role of gut integrity in mitigating long-term effects of ELS.
Original reference: Castro-Zavala, A. et al. Behav. Brain Res. 495, 115772 (2025)
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