RT Journal Article
T1 A persistent increase in gut permeability correlates with emotional dysregulation following maternal separation in male and female mice
A1 Castro-Zavala, Adriana
A1 Nieto-Nieves, Ana
A1 Melgar-Locatelli, Sonia
A1 Medina-Rodríguez, Lidia
A1 Mañas-Padilla, María del Carmen
A1 Castilla-Ortega, María Estela
K1 Ansiedad de separación en niños
K1 Intestinos -- Microbiología
K1 Emociones
K1 Afecto (Psicología)
AB Early life stress (ELS) significantly influences vulnerability to psychiatric disorders in adulthood. A widely used preclinical model for studying ELS is maternal separation with early weaning (MSEW), which mimics early-life neglect. This study evaluated the impact of ELS induced by MSEW on emotional behaviour, intestinal permeability, and neuroinflammatory markers in male and female mice. Our results show that MSEW increases anxietylike behaviours in adulthood, particularly in females, and exacerbates depression-like behaviours and anhedonia in both sexes. Notably, increased intestinal permeability correlated with higher anxiety and depression-like responses, suggesting a crucial role of gut health in emotional regulation. These alterations were long-lasting, indicating persistent effects on gut function following ELS. Additionally, MSEW animals exhibited higher hippocampalBDNF expression, particularly males. However, there were no significant differences in the long-termsurvival of adult-born hippocampal cells, as indicated by BrdU+ labelling. Both sexes showed increased NF-κBprotein levels; however, only MSEW males exhibited TNF-α changes, suggesting a sex-specific regulatorymechanism in response to chronic stress. This study highlights intestinal permeability as a key mechanismlinking ELS to emotional and behavioural dysregulation. By demonstrating a long-lasting increase in intestinalpermeability and its correlation with mood disorders, our findings extend the gut-brain axis hypothesis to ELS.The inclusion of both sexes provides a more comprehensive understanding of sex-specific effects of early stress,often overlooked in previous research.
PB Elsevier
YR 2025
FD 2025-08
LK https://hdl.handle.net/10630/40028
UL https://hdl.handle.net/10630/40028
LA eng
NO Castro-Zavala A, Nieto-Nieves AE, Melgar-Locatelli S, Medina-Rodríguez L, Mañas-Padilla MC, Castilla-Ortega E. A persistent increase in gut permeability correlates with emotional dysregulation following maternal separation in male and female mice. Behav Brain Res. 2025 Oct 18;495:115772. doi: 10.1016/j.bbr.2025.115772. Epub 2025 Aug 8.
NO This study was funded by Grant PID2020–114374RB-I00 from MCIN/AEI/10.13039/501100011033 (to E.C-O.), Universidad de M´alaga (B.1. Ayudas para proyectos dirigidos por j´ovenes investigadores B1–2022_05 to A.C.-Z,), and Universidad de M´alaga (C.2. II Plan Propio de Investigaci´on, Transferencia y Divulgaci´on Científica). Funding for open access charge: Universidad de M´alaga / CBUA. A.C.Z. holds a postdoctoral research contract from the Secretaría General de Universidades, Investigaci´on y Tecnología–Junta de Andalucía (DOC21_00365) and a Sara Borrell contract from the Instituto de Salud Carlos III (CD24/00041). A.N.-N. holds a predoctoral grant from the Spanish Ministry of Science, Innovation and Universities (FPU22/ 02044).
NO Funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026