敲除 FAME4-associating YEATS2 会损害黑腹果蝇多巴胺能突触的完整性并导致癫痫样行为

IF 6.7 2区 医学 Q1 NEUROSCIENCES Progress in Neurobiology Pub Date : 2023-12-20 DOI:10.1016/j.pneurobio.2023.102558
Luca Lo Piccolo , Ranchana Yeewa , Sureena Pohsa , Titaree Yamsri , Daniel Calovi , Jutarop Phetcharaburanin , Manida Suksawat , Thanaporn Kulthawatsiri , Vorasuk Shotelersuk , Salinee Jantrapirom
{"title":"敲除 FAME4-associating YEATS2 会损害黑腹果蝇多巴胺能突触的完整性并导致癫痫样行为","authors":"Luca Lo Piccolo ,&nbsp;Ranchana Yeewa ,&nbsp;Sureena Pohsa ,&nbsp;Titaree Yamsri ,&nbsp;Daniel Calovi ,&nbsp;Jutarop Phetcharaburanin ,&nbsp;Manida Suksawat ,&nbsp;Thanaporn Kulthawatsiri ,&nbsp;Vorasuk Shotelersuk ,&nbsp;Salinee Jantrapirom","doi":"10.1016/j.pneurobio.2023.102558","DOIUrl":null,"url":null,"abstract":"<div><p><span>Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a </span><em>TTTTA/TTTCA</em> intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene <em>YEATS2</em>. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons. This study used <em>Drosophila</em> to explore the effects of reducing <em>YEATS2</em> expression. Two pan-neuronally driven <em>dsDNA</em> were used for knockdown of <em>Drosophila YEATS2</em> (<em>dYEATS2</em>), and the resulting molecular and behavioural outcomes were evaluated. <em>Drosophila</em> with reduced <em>dYEATS2</em> expression exhibited decreased tolerance to acute stress, disturbed locomotion, abnormal social behaviour, and decreased motivated activity. Additionally, reducing <em>dYEATS2</em> expression negatively affected <span><em>tyrosine hydroxylase</em></span> (<em>TH</em><span>) gene expression, resulting in decreased dopamine biosynthesis. Remarkably, seizure-like behaviours induced by knocking down </span><em>dYEATS2</em><span> were rescued by the administration of L-DOPA. This study reveals a novel role of YEATS2 in neurons in regulating acute stress responses, locomotion, and complex behaviours, and suggests that haploinsufficiency of YEATS2 may play a role in FAME4.</span></p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FAME4-associating YEATS2 knockdown impairs dopaminergic synaptic integrity and leads to seizure-like behaviours in Drosophila melanogaster\",\"authors\":\"Luca Lo Piccolo ,&nbsp;Ranchana Yeewa ,&nbsp;Sureena Pohsa ,&nbsp;Titaree Yamsri ,&nbsp;Daniel Calovi ,&nbsp;Jutarop Phetcharaburanin ,&nbsp;Manida Suksawat ,&nbsp;Thanaporn Kulthawatsiri ,&nbsp;Vorasuk Shotelersuk ,&nbsp;Salinee Jantrapirom\",\"doi\":\"10.1016/j.pneurobio.2023.102558\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a </span><em>TTTTA/TTTCA</em> intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene <em>YEATS2</em>. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons. This study used <em>Drosophila</em> to explore the effects of reducing <em>YEATS2</em> expression. Two pan-neuronally driven <em>dsDNA</em> were used for knockdown of <em>Drosophila YEATS2</em> (<em>dYEATS2</em>), and the resulting molecular and behavioural outcomes were evaluated. <em>Drosophila</em> with reduced <em>dYEATS2</em> expression exhibited decreased tolerance to acute stress, disturbed locomotion, abnormal social behaviour, and decreased motivated activity. Additionally, reducing <em>dYEATS2</em> expression negatively affected <span><em>tyrosine hydroxylase</em></span> (<em>TH</em><span>) gene expression, resulting in decreased dopamine biosynthesis. Remarkably, seizure-like behaviours induced by knocking down </span><em>dYEATS2</em><span> were rescued by the administration of L-DOPA. This study reveals a novel role of YEATS2 in neurons in regulating acute stress responses, locomotion, and complex behaviours, and suggests that haploinsufficiency of YEATS2 may play a role in FAME4.</span></p></div>\",\"PeriodicalId\":20851,\"journal\":{\"name\":\"Progress in Neurobiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2023-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in Neurobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0301008223001594\",\"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":"Progress in Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0301008223001594","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

家族性成人肌阵挛癫痫(FAME)是一种由 TTTTA/TTTCA 内含子重复扩增引起的神经系统疾病。FAME4 是由基因 YEATS2 第一个内含子的重复扩增导致的六种 FAME 类型之一。虽然 RNA 毒性被认为是 FAME 的主要机制,但重复扩增所在基因的作用仍不清楚,尤其是 YEATS2 在神经元中的作用。本研究利用果蝇来探索减少 YEATS2 表达的影响。研究使用了两种泛神经元驱动的dsDNA来敲除果蝇YEATS2(dYEATS2),并评估了由此产生的分子和行为结果。dYEATS2 表达减少的果蝇表现出对急性应激的耐受性降低、运动紊乱、社交行为异常和动机活动减少。此外,减少 dYEATS2 的表达还会对酪氨酸羟化酶(TH)基因的表达产生负面影响,导致多巴胺的生物合成减少。值得注意的是,敲除 dYEATS2 所诱发的癫痫样行为可通过服用 L-DOPA 得到挽救。这项研究揭示了YEATS2在神经元中调节急性应激反应、运动和复杂行为的新作用,并表明YEATS2的单倍体缺陷可能在FAME4中发挥作用。
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
FAME4-associating YEATS2 knockdown impairs dopaminergic synaptic integrity and leads to seizure-like behaviours in Drosophila melanogaster

Familial adult myoclonus epilepsy (FAME) is a neurological disorder caused by a TTTTA/TTTCA intronic repeat expansion. FAME4 is one of the six types of FAME that results from the repeat expansion in the first intron of the gene YEATS2. Although the RNA toxicity is believed to be the primary mechanism underlying FAME, the role of genes where repeat expansions reside is still unclear, particularly in the case of YEATS2 in neurons. This study used Drosophila to explore the effects of reducing YEATS2 expression. Two pan-neuronally driven dsDNA were used for knockdown of Drosophila YEATS2 (dYEATS2), and the resulting molecular and behavioural outcomes were evaluated. Drosophila with reduced dYEATS2 expression exhibited decreased tolerance to acute stress, disturbed locomotion, abnormal social behaviour, and decreased motivated activity. Additionally, reducing dYEATS2 expression negatively affected tyrosine hydroxylase (TH) gene expression, resulting in decreased dopamine biosynthesis. Remarkably, seizure-like behaviours induced by knocking down dYEATS2 were rescued by the administration of L-DOPA. This study reveals a novel role of YEATS2 in neurons in regulating acute stress responses, locomotion, and complex behaviours, and suggests that haploinsufficiency of YEATS2 may play a role in FAME4.

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
Progress in Neurobiology
Progress in Neurobiology 医学-神经科学
CiteScore
12.80
自引率
1.50%
发文量
107
审稿时长
33 days
期刊介绍: Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.
期刊最新文献
Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2ALS phenotypes in Drosophila melanogaster Neuronal threshold functions: Determining symptom onset in neurological disorders
×
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