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Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress

Year: 2025

Type: article

Abstract: BACKGROUND: Childhood is a crucial period for brain development, and short-term juvenile stress has demonstrated long-lasting effects on cognitive and cellular functions in the hippocampus. However, the influence of such stress on the brain's overall network remains unclear. METHODS: In this study, we employed functional magnetic resonance imaging (fMRI) to explore the effects of transient wild stress on juvenile male rats. Pregnant rats were purchased and housed in a specific pathogen-free (SPF) environment, with pups separated by sex on postnatal day 21 (PD21). From PD27 to PD29, male rats were subjected to transient wild stress, which included forced swimming, elevated platform exposure, and restraint stress. Following stress exposure, all animals were carefully maintained and scanned at 42 days of age (PD42) using fMRI. Structural analysis was performed using voxel-based morphometry (VBM) to assess changes in gray matter volume, while functional activity was evaluated through regional homogeneity (ReHo) and voxel-wise functional connectivity. RESULTS: The results showed significant reductions in gray matter volume in several brain regions in the stress group, including the periaqueductal gray (PAG), entorhinal cortex (Ent), and dentate gyrus (DG). In terms of functional activity, cortical regions, particularly the primary somatosensory areas, exhibited decreased activity, whereas increased activity was observed in the PAG, DG, and medulla. Furthermore, functional connectivity analysis revealed a significant reduction in connectivity between the DG and entorhinal cortex, while the DG-PAG connectivity was significantly enhanced. CONCLUSIONS: These findings suggest that juvenile stress leads to profound alterations in both brain structure and function, potentially disrupting emotional regulation and memory processing by affecting the development and connectivity of key brain regions.

Source: Brain Sciences

DOI: 10.3390/brainsci15030284

Authors: Aoling Cai, Danhao Zheng, Fanyong Xu, Fei Wang, Sreedharan Sajikumar, Jie Wang