Exosomes Derived from DPA-treated UCMSCs Attenuated Depression-like Behaviors and Neuroinflammation in a Model of Depression Induced by Chronic Stress.

Peng Li, Fucheng Zhang, Chengyi Huang, Cai Zhang, Zhiyou Yang, Yongping Zhang, Cai Song
{"title":"Exosomes Derived from DPA-treated UCMSCs Attenuated Depression-like Behaviors and Neuroinflammation in a Model of Depression Induced by Chronic Stress.","authors":"Peng Li, Fucheng Zhang, Chengyi Huang, Cai Zhang, Zhiyou Yang, Yongping Zhang, Cai Song","doi":"10.1007/s11481-024-10154-6","DOIUrl":null,"url":null,"abstract":"<p><p>Depression is characterized by both neuroinflammation and neurodegeneration. Exosomes (Exo) have been shown to function as inhibitors of inflammation and promoters of neurogenesis. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid, can combat depression by increasing levels of docosapentaenoic acid (DPA). This study explored the effects of DPA on the therapeutic potential of Exo derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in glia-induced neuroinflammation associated with depression. Exposure to chronic unpredictable mild stress (CUMS) over six weeks induced depression- and anxiety-like behaviors, while decreasing the levels of serotonin and dopamine. Molecularly, CUMS increased the concentrations of the microglial M1 markers Iba1, iNOS, and IL-1β, while reducing the M2 markers Arg1, CD206, and IL-10 in the prefrontal cortex and hippocampus. However, Exo therapy reversed these effects. Moreover, DPA treatment of Exo demonstrated superior efficacy in alleviating depressive behaviors, neurotransmitter deficiencies, and M1 microglial activation. In vitro, Exo suppressed LPS-stimulated BV2 cell viability and M1 microglial activation, while mitigating the SH-SY5Y cell apoptosis triggered by treatment with the conditioned medium from LPS-activated BV2 cells. Furthermore, administration of DPA enhanced this effect. Mechanically, DPA enhanced Exo function by upregulating miR125b-5p expression, thereby targeting the MyD88/TRAF6/NF-κB signaling pathway. In summary, Exo exhibited antidepressant effects by suppressing M1 microglial neuroinflammation, while DPA treatment provided a more potent therapeutic effect on depression-like changes through the upregulation of miR125b-5p targeting the MyD88/TRAF6/NF-κB pathway.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"19 1","pages":"55"},"PeriodicalIF":6.2000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s11481-024-10154-6","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Depression is characterized by both neuroinflammation and neurodegeneration. Exosomes (Exo) have been shown to function as inhibitors of inflammation and promoters of neurogenesis. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid, can combat depression by increasing levels of docosapentaenoic acid (DPA). This study explored the effects of DPA on the therapeutic potential of Exo derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in glia-induced neuroinflammation associated with depression. Exposure to chronic unpredictable mild stress (CUMS) over six weeks induced depression- and anxiety-like behaviors, while decreasing the levels of serotonin and dopamine. Molecularly, CUMS increased the concentrations of the microglial M1 markers Iba1, iNOS, and IL-1β, while reducing the M2 markers Arg1, CD206, and IL-10 in the prefrontal cortex and hippocampus. However, Exo therapy reversed these effects. Moreover, DPA treatment of Exo demonstrated superior efficacy in alleviating depressive behaviors, neurotransmitter deficiencies, and M1 microglial activation. In vitro, Exo suppressed LPS-stimulated BV2 cell viability and M1 microglial activation, while mitigating the SH-SY5Y cell apoptosis triggered by treatment with the conditioned medium from LPS-activated BV2 cells. Furthermore, administration of DPA enhanced this effect. Mechanically, DPA enhanced Exo function by upregulating miR125b-5p expression, thereby targeting the MyD88/TRAF6/NF-κB signaling pathway. In summary, Exo exhibited antidepressant effects by suppressing M1 microglial neuroinflammation, while DPA treatment provided a more potent therapeutic effect on depression-like changes through the upregulation of miR125b-5p targeting the MyD88/TRAF6/NF-κB pathway.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
经 DPA 处理的 UCMSCs 外泌体可减轻慢性压力诱导的抑郁模型中的抑郁样行为和神经炎症。
抑郁症的特征是神经炎症和神经变性。研究表明,外泌体(Exo)具有抑制炎症和促进神经发生的功能。欧米伽-3 多不饱和脂肪酸(如二十碳五烯酸)可以通过提高二十二碳五烯酸(DPA)的水平来对抗抑郁症。本研究探讨了DPA对人脐带间充质干细胞(hUCMSCs)提取的Exo在胶质细胞诱导的与抑郁症相关的神经炎症中的治疗潜力的影响。六周的慢性不可预测轻度应激(CUMS)会诱发抑郁和焦虑行为,同时降低血清素和多巴胺的水平。从分子角度看,CUMS增加了前额叶皮层和海马中小胶质细胞M1标记物Iba1、iNOS和IL-1β的浓度,同时降低了M2标记物Arg1、CD206和IL-10的浓度。然而,Exo疗法逆转了这些影响。此外,Exo 的 DPA 治疗在减轻抑郁行为、神经递质缺乏和 M1 微神经胶质细胞活化方面表现出卓越的疗效。在体外,Exo 可抑制 LPS 刺激的 BV2 细胞活力和 M1 小神经胶质细胞活化,同时减轻 LPS 激活的 BV2 细胞条件培养基处理引发的 SH-SY5Y 细胞凋亡。此外,服用 DPA 还能增强这种效果。在机制上,DPA通过上调miR125b-5p的表达增强了Exo的功能,从而靶向MyD88/TRAF6/NF-κB信号通路。总之,Exo通过抑制M1小胶质细胞神经炎症表现出抗抑郁作用,而DPA治疗则通过上调靶向MyD88/TRAF6/NF-κB通路的miR125b-5p对抑郁症样改变产生了更强的治疗效果。
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 去求助
来源期刊
自引率
0.00%
发文量
0
期刊介绍:
期刊最新文献
Matrix Metalloproteinase-9 Signaling Regulates Colon Barrier Integrity in Models of HIV Infection. Vitamin K2 Ameliorates Diabetes-Associated Cognitive Decline by Reducing Oxidative Stress and Neuroinflammation. Exosomes Derived from DPA-treated UCMSCs Attenuated Depression-like Behaviors and Neuroinflammation in a Model of Depression Induced by Chronic Stress. Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury. Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/β-endorphin Signaling in the Spinal Cord of Rats.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1