复合B族维生素通过抑制海马线粒体DNA甲基化，减轻大鼠单次长时间应激诱导的创伤后应激障碍样行为

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology Pub Date : 2025-01-17 DOI:10.1016/j.jnrt.2025.100187

Yanteng Li , Runzi Wang , Fang Xie , Lingjia Qian , Yong Zhang , Jianning Zhang

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引用次数: 0

摘要

创伤后应激障碍（PTSD）是一种严重的精神障碍。目前的治疗方法，通常使用血清素再摄取抑制剂，效果有限，经常引起严重的不良反应。本研究旨在探讨复合B族维生素（VBco）对单次延长应激（SPS）大鼠创伤后应激样行为的保护作用及其可能的分子机制。方法80只成年雄性大鼠随机分为4组（n = 20）：对照组（CTRL）、SPS + VBco对照组（CTRL-VBco）和SPS + VBco组（SPS-VBco）。建模完成后，进行行为学测试（包括空地测试、强迫游泳测试、蔗糖偏好测试、恐惧条件反射测试）。采集血液检测血浆同型半胱氨酸（Hcy）浓度。采集脑组织进行线粒体功能分析、western blotting和实时定量聚合酶链反应（PCR）。结果vbco可显著降低sps后1周血浆Hcy水平。SPS-VBco组小鼠在开阔场地试验中梳洗次数减少，运动速度加快，在强迫游泳试验中休息时间减少，在蔗糖偏好试验中蔗糖偏好比增加，在恐惧条件反射试验中冻结时间减少。VBco增加了海马线粒体呼吸链相关蛋白亚基mRNA的表达，改善了海马线粒体复合体I和IV的活性和膜电位。VBco逆转了sps诱导的海马线粒体mtND1和mtND3甲基化。VBco下调海马线粒体甲基转移酶（DNMT1、DNMT3A、DNMT3B）水平。结论茯苓多糖可有效抑制海马线粒体DNA甲基化。这可能是它减轻类似创伤后应激障碍行为的机制之一。

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Compound B vitamins mitigate post-traumatic stress disorder-like behaviors induced by single prolonged stress in rats by inhibiting hippocampal mitochondrial DNA methylation

Background

Post-traumatic stress disorder (PTSD) is a serious mental disorder. Current treatments, typically using serotonin reuptake inhibitors, have limited effectiveness and often cause severe adverse effects. In the present study, we investigated whether Compound B vitamins (VBco) have protective effects in improving PTSD-like behaviors and the possible related molecular mechanisms in a rat model of single prolonged stress (SPS).

Methods

Eighty adult male rats were randomly divided into four groups (n = 20): control (CTRL), SPS, VBco control (CTRL-VBco), and SPS and VBco (SPS-VBco). After modeling, behavioral tests (including open field test, forced swimming test, sucrose preference test, fear conditioning test) were conducted. Blood was collected to detect plasma homocysteine (Hcy) concentrations. Brain tissue was collected for mitochondrial function analysis, western blotting, and quantitative real-time Polymerase Chain Reaction (PCR).

Results

VBco reduced plasma Hcy levels significantly 1 week post-SPS. The SPS-VBco group showed decreased grooming times and increased movement speed in the open field test, less resting time in the forced swim test, increased sucrose preference ratios in the sucrose preference test, and less freezing time in the fear conditioning test. VBco increased the expression of mRNA for subunits of respiratory chain-related protein in hippocampal mitochondria and improved mitochondrial complex I and IV activity and membrane potential in hippocampus. VBco reversed SPS-induced mtND1 and mtND3 methylation in hippocampal mitochondria. VBco downregulated the levels of methyltransferases (DNMT1, DNMT3A, DNMT3B) in hippocampal mitochondria.