Molecular hydrogen inhibits neuroinflammation and ameliorates depressive-like behaviors and short-term cognitive impairment in senescence-accelerated mouse prone 8 mice

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-11-08 DOI:10.1016/j.bbr.2024.115330

Keiichi Nakagawa , Kayoko Kodama , Wataru Nagata , Sayaka Takahashi , Yasushi Satoh , Toshiaki Ishizuka

{"title":"Molecular hydrogen inhibits neuroinflammation and ameliorates depressive-like behaviors and short-term cognitive impairment in senescence-accelerated mouse prone 8 mice","authors":"Keiichi Nakagawa , Kayoko Kodama , Wataru Nagata , Sayaka Takahashi , Yasushi Satoh , Toshiaki Ishizuka","doi":"10.1016/j.bbr.2024.115330","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><div>Neuroinflammation, a low-grade chronic inflammation of the central nervous system, is linked to age-related neuropsychiatric disorders such as senile depression and Alzheimer's disease. Recent studies have explored controlling neuroinflammation as a novel treatment strategy. Molecular hydrogen shows anti-inflammatory effects. However, its impacts on neuroinflammation and age-related neuropsychiatric disorders remain unelucidated. We investigated molecular hydrogen’s effects on microglial activation, neuroinflammation, depressive-like behavior, and short-term cognitive decline in senescence-accelerated mouse-prone 8 (SAMP8) mice.</div></div><div><h3>Methods</h3><div>Six-week-old SAMP8 or senescence-accelerated mouse-resistant 1 (SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26–28 weeks. Depressive-like behavior was assessed using tail suspension and forced swimming tests, while cognitive function was evaluated using the Y-maze and object recognition tests. Brain tissues were used for immunohistochemical studies or to measure pro-inflammatory cytokine levels via enzyme-linked immunosorbent assay (ELISA).</div></div><div><h3>Results</h3><div>HRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice. Additionally, HRJ intake suppressed the 8-hydroxy-2′-deoxyguanosine (8-OHdG), Iba1, and cleaved caspase 3 expression levels in the medial prefrontal cortex and hippocampal dentate gyrus. Furthermore, HRJ intake significantly lowered IL-6 levels in brain tissues of SAMP8 mice.</div></div><div><h3>Conclusions</h3><div>These findings suggest that molecular hydrogen treatment may regulate neuroinflammation induced by activated microglia and improve depressive-like behavior and short-term cognitive impairment in SAMP8 mice.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"478 ","pages":"Article 115330"},"PeriodicalIF":2.6000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166432824004868","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Background and aims

Neuroinflammation, a low-grade chronic inflammation of the central nervous system, is linked to age-related neuropsychiatric disorders such as senile depression and Alzheimer's disease. Recent studies have explored controlling neuroinflammation as a novel treatment strategy. Molecular hydrogen shows anti-inflammatory effects. However, its impacts on neuroinflammation and age-related neuropsychiatric disorders remain unelucidated. We investigated molecular hydrogen’s effects on microglial activation, neuroinflammation, depressive-like behavior, and short-term cognitive decline in senescence-accelerated mouse-prone 8 (SAMP8) mice.

Methods

Six-week-old SAMP8 or senescence-accelerated mouse-resistant 1 (SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26–28 weeks. Depressive-like behavior was assessed using tail suspension and forced swimming tests, while cognitive function was evaluated using the Y-maze and object recognition tests. Brain tissues were used for immunohistochemical studies or to measure pro-inflammatory cytokine levels via enzyme-linked immunosorbent assay (ELISA).

Results

HRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice. Additionally, HRJ intake suppressed the 8-hydroxy-2′-deoxyguanosine (8-OHdG), Iba1, and cleaved caspase 3 expression levels in the medial prefrontal cortex and hippocampal dentate gyrus. Furthermore, HRJ intake significantly lowered IL-6 levels in brain tissues of SAMP8 mice.

Conclusions

These findings suggest that molecular hydrogen treatment may regulate neuroinflammation induced by activated microglia and improve depressive-like behavior and short-term cognitive impairment in SAMP8 mice.

查看原文本刊更多论文

分子氢能抑制神经炎症，改善衰老加速小鼠易感基因 8 小鼠的抑郁样行为和短期认知障碍。

背景和目的：神经炎症是中枢神经系统的一种低度慢性炎症，与老年性抑郁症和阿尔茨海默病等与年龄相关的神经精神疾病有关。最近的研究将控制神经炎症作为一种新的治疗策略。分子氢具有抗炎作用。然而，它对神经炎症和老年相关神经精神疾病的影响仍未得到阐明。我们研究了分子氢对衰老加速小鼠易感基因 8（SAMP8）小鼠的小胶质细胞活化、神经炎症、抑郁样行为和短期认知能力下降的影响：六周龄的SAMP8或衰老加速小鼠抗性1（SAMR1）小鼠从六周龄开始接受富氢果冻（HRJ）或安慰剂果冻（PJ），持续26-28周。抑郁样行为通过尾悬吊和强迫游泳测试进行评估，认知功能通过Y-迷宫和物体识别测试进行评估。脑组织用于免疫组化研究，或通过酶联免疫吸附试验（ELISA）测量促炎细胞因子的水平：结果：摄入HRJ可减少SAMP8小鼠在尾悬浮和强迫游泳测试中的不动时间，并增强其视觉认知能力和空间工作记忆。此外，摄入 HRJ 可抑制内侧前额叶皮层和海马齿状回中的 8-羟基-2'-脱氧鸟苷（8-OHdG）、Iba1 和裂解 Caspase 3 的表达水平。此外，摄入氢气还能显著降低 SAMP8 小鼠脑组织中 IL-6 的水平：这些研究结果表明，分子氢治疗可调节活化小胶质细胞诱导的神经炎症，改善 SAMP8 小鼠的抑郁样行为和短期认知障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.