α -突触核蛋白原纤维抑制mPFC中BDNF/ERK信号回路的激活,诱导帕金森病样改变伴抑郁症

IF 5.9 2区 医学 Q1 NEUROSCIENCES Neuroscience bulletin Pub Date : 2024-11-28 DOI:10.1007/s12264-024-01323-x
Zhuoran Ma, Yan Xu, Piaopiao Lian, Yi Wu, Ke Liu, Zhaoyuan Zhang, Zhicheng Tang, Xiaoman Yang, Xuebing Cao
{"title":"α -突触核蛋白原纤维抑制mPFC中BDNF/ERK信号回路的激活,诱导帕金森病样改变伴抑郁症","authors":"Zhuoran Ma, Yan Xu, Piaopiao Lian, Yi Wu, Ke Liu, Zhaoyuan Zhang, Zhicheng Tang, Xiaoman Yang, Xuebing Cao","doi":"10.1007/s12264-024-01323-x","DOIUrl":null,"url":null,"abstract":"<p><p>Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.\",\"authors\":\"Zhuoran Ma, Yan Xu, Piaopiao Lian, Yi Wu, Ke Liu, Zhaoyuan Zhang, Zhicheng Tang, Xiaoman Yang, Xuebing Cao\",\"doi\":\"10.1007/s12264-024-01323-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.</p>\",\"PeriodicalId\":19314,\"journal\":{\"name\":\"Neuroscience bulletin\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-11-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroscience bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12264-024-01323-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12264-024-01323-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

抑郁(Dep)是帕金森病(PD)最常见的伴随症状之一,但PD-Dep的发生缺乏详细的病理证据。目前,从这两种情况的症状管理使用传统的药理学干预仍然是一个艰巨的任务。在本研究中,我们发现PD-Dep大鼠内侧前额叶皮层(mPFC)细胞外信号相关激酶(ERK)激活受损,转录和翻译水平降低,脑源性神经营养因子(BDNF)表达降低。我们证明了α-突触核蛋白(pS129)的异常磷酸化诱导原肌球蛋白相关激酶受体B型(TrkB)在神经元细胞膜上的保留,导致BDNF/TrkB信号功能障碍。我们选择SEW2871作为上调ERK磷酸化的改善剂。结果显示,PD- dep大鼠PD和抑郁的行为表现均有改善。此外,pS129的减少伴随着pd - deep大鼠mPFC中BDNF/ERK信号回路功能的恢复。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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
Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Neuroscience bulletin
Neuroscience bulletin NEUROSCIENCES-
CiteScore
7.20
自引率
16.10%
发文量
163
审稿时长
6-12 weeks
期刊介绍: Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.
期刊最新文献
Mapping Fear-Related Neural Activity and Circuitry Changes Following Prophylactic Administration of (R,S)-Ketamine and (2S,6S)-Hydroxynorketamine. Non-invasive Modulation of Deep Brain Nuclei by Temporal Interference Stimulation. Zona Incerta: A Bridge for Infant-Mother Interaction. Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders. Triple-Target Inhibition of Cholinesterase, Amyloid Aggregation, and GSK3β to Ameliorate Cognitive Deficits and Neuropathology in the Triple-Transgenic Mouse Model of Alzheimer's Disease.
×
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