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

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,...

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Main Authors: Aoling Cai, Danhao Zheng, Fanyong Xu, Fei Wang, Sreedharan Sajikumar, Jie Wang
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/15/3/284
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author Aoling Cai
Danhao Zheng
Fanyong Xu
Fei Wang
Sreedharan Sajikumar
Jie Wang
author_facet Aoling Cai
Danhao Zheng
Fanyong Xu
Fei Wang
Sreedharan Sajikumar
Jie Wang
author_sort Aoling Cai
collection DOAJ
description 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.
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spelling doaj-art-77c8ac5b5cb34681807cf7eafa5a203a2025-08-20T03:43:21ZengMDPI AGBrain Sciences2076-34252025-03-0115328410.3390/brainsci15030284Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile StressAoling Cai0Danhao Zheng1Fanyong Xu2Fei Wang3Sreedharan Sajikumar4Jie Wang5Department of Radiology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, ChinaDepartment of Radiology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, ChinaDepartment of Radiology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, ChinaEarly Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Physiology, National University of Singapore, Singapore 117593, SingaporeDepartment of Radiology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, ChinaBackground: 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.https://www.mdpi.com/2076-3425/15/3/284juvenile stressbrain developmentfMRIbrain volumecognitive function
spellingShingle Aoling Cai
Danhao Zheng
Fanyong Xu
Fei Wang
Sreedharan Sajikumar
Jie Wang
Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress
Brain Sciences
juvenile stress
brain development
fMRI
brain volume
cognitive function
title Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress
title_full Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress
title_fullStr Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress
title_full_unstemmed Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress
title_short Variations of Aberrant Volume, Activity, and Network Connectivity of Hippocampus in Adolescent Male Rats Exposed to Juvenile Stress
title_sort variations of aberrant volume activity and network connectivity of hippocampus in adolescent male rats exposed to juvenile stress
topic juvenile stress
brain development
fMRI
brain volume
cognitive function
url https://www.mdpi.com/2076-3425/15/3/284
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