Breakdown of the blood-brain barrier in depressed mice induced by chronic unpredictable mild stress

IF 3.7 2区 医学 Q1 PSYCHIATRY
Wei Shi , Shan Zhang , Kaihu Yao , Qinghong Meng , Yujia Lu , Yi Ren , Li Li , Jingjie Zhao
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Abstract

Background

Recent studies have suggested potential impairment of the blood-brain barrier (BBB) in depression. However, due to the limited research and variability in animal models, further investigation using diverse and stable models is necessary.

Methods

A male mouse model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Following model establishment, depression-like behaviors were assessed using the sucrose preference test, tail suspension test, and forced swimming test. Morphological changes in the hippocampus were examined through hematoxylin-eosin staining. BBB permeability was evaluated using the Evans blue leakage test, fluorescein sodium (NaF) leakage test, and serum S100B content assessment. Gene and protein expression levels of BBB-related proteins in the hippocampus were determined via real-time PCR, western blotting, and immunofluorescence assays.

Results

CUMS exposure induced depression-like behaviors, including reduced body weight gain, diminished sucrose preference, and prolonged immobility in both the tail suspension test and forced swimming test. While no significant pathological changes were observed in the hippocampus of either group, increased BBB permeability was noted in the CUMS group, as evidenced by enhanced NaF leakage into the brain parenchyma and elevated serum S100B levels. Gene expression analysis revealed downregulation of angiogenesis-related genes and tight junction proteins in the CUMS group. Additionally, protein levels of tight junction proteins Claudin-5 and ZO-1 were lower in the CUMS group compared to controls.

Limitations

This study is limited to a male mouse model, and the BBB in females is worth exploring in the future.

Conclusions

Increased BBB permeability and decreased expression of tight junction proteins Claudin5 and ZO-1 were observed in mice with CUMS-induced depression.
慢性不可预测轻度应激诱发抑郁小鼠血脑屏障破裂
背景最近的研究表明,抑郁症可能会损害血脑屏障(BBB)。方法采用慢性不可预知的轻度应激(CUMS)方案建立了雄性抑郁症小鼠模型。建立模型后,使用蔗糖偏好试验、尾悬挂试验和强迫游泳试验对类似抑郁的行为进行了评估。通过苏木精-伊红染色检查海马的形态变化。使用伊文思蓝渗漏试验、荧光素钠(NaF)渗漏试验和血清 S100B 含量评估来评价 BBB 的通透性。通过实时 PCR、Western 印迹和免疫荧光检测确定了海马中 BBB 相关蛋白的基因和蛋白表达水平。结果CUMS 暴露会诱发类似抑郁的行为,包括体重增加减少、蔗糖偏好降低以及在尾悬试验和强迫游泳试验中长时间不动。虽然两组的海马均未观察到明显的病理变化,但CUMS组的BBB通透性增加,表现为NaF渗漏到脑实质的增加和血清S100B水平的升高。基因表达分析显示,CUMS 组血管生成相关基因和紧密连接蛋白下调。此外,与对照组相比,CUMS组紧密连接蛋白Claudin-5和ZO-1的蛋白水平较低。结论在CUMS诱导的抑郁症小鼠中观察到BBB通透性增加,紧密连接蛋白Claudin5和ZO-1表达减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of psychiatric research
Journal of psychiatric research 医学-精神病学
CiteScore
7.30
自引率
2.10%
发文量
622
审稿时长
130 days
期刊介绍: Founded in 1961 to report on the latest work in psychiatry and cognate disciplines, the Journal of Psychiatric Research is dedicated to innovative and timely studies of four important areas of research: (1) clinical studies of all disciplines relating to psychiatric illness, as well as normal human behaviour, including biochemical, physiological, genetic, environmental, social, psychological and epidemiological factors; (2) basic studies pertaining to psychiatry in such fields as neuropsychopharmacology, neuroendocrinology, electrophysiology, genetics, experimental psychology and epidemiology; (3) the growing application of clinical laboratory techniques in psychiatry, including imagery and spectroscopy of the brain, molecular biology and computer sciences;
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