Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity

IF 6.7 2区 医学 Q1 NEUROSCIENCES Progress in Neurobiology Pub Date : 2024-01-10 DOI:10.1016/j.pneurobio.2024.102568
Xingliang Zhu , Yuyoung Joo , Simone Bossi , Ross A. McDevitt , Aoji Xie , Yue Wang , Yutong Xue , Shuaikun Su , Seung Kyu Lee , Nirnath Sah , Shiliang Zhang , Rong Ye , Alejandro Pinto , Yongqing Zhang , Kimi Araki , Masatake Araki , Marisela Morales , Mark P. Mattson , Henriette van Praag , Weidong Wang
{"title":"Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity","authors":"Xingliang Zhu ,&nbsp;Yuyoung Joo ,&nbsp;Simone Bossi ,&nbsp;Ross A. McDevitt ,&nbsp;Aoji Xie ,&nbsp;Yue Wang ,&nbsp;Yutong Xue ,&nbsp;Shuaikun Su ,&nbsp;Seung Kyu Lee ,&nbsp;Nirnath Sah ,&nbsp;Shiliang Zhang ,&nbsp;Rong Ye ,&nbsp;Alejandro Pinto ,&nbsp;Yongqing Zhang ,&nbsp;Kimi Araki ,&nbsp;Masatake Araki ,&nbsp;Marisela Morales ,&nbsp;Mark P. Mattson ,&nbsp;Henriette van Praag ,&nbsp;Weidong Wang","doi":"10.1016/j.pneurobio.2024.102568","DOIUrl":null,"url":null,"abstract":"<div><p>The <u>Top</u>oisomerase <u>3B</u> (Top3b) - <u>T</u>u<u>d</u>o<u>r d</u>omain containing <u>3</u><span> (Tdrd3) protein complex is the only dual-activity topoisomerase complex that can alter both DNA and RNA topology in animals. </span><em>TOP3B</em><span> mutations in humans are associated with schizophrenia<span><span>, autism and </span>cognitive disorders; and </span></span><em>Top3b</em><span>-null mice exhibit several phenotypes observed in animal models of psychiatric and cognitive disorders, including impaired cognitive and emotional behaviors<span>, aberrant neurogenesis<span> and synaptic plasticity, and transcriptional defects. Similarly, human </span></span></span><em>TDRD3</em> genomic variants have been associated with schizophrenia, verbal short-term memory and educational attainment. However, the importance of <em>Tdrd3</em> in normal brain function has not been examined in animal models. Here we generated a <em>Tdrd3</em>-null mouse strain and demonstrate that these mice display both shared and unique defects when compared to <em>Top3b-</em>null mice. Shared defects were observed in cognitive behaviors, synaptic plasticity, adult neurogenesis, newborn neuron morphology, and neuronal activity-dependent transcription; whereas defects unique to <em>Tdrd3</em><span><span>-deficient mice include hyperactivity, changes in anxiety-like behaviors, olfaction<span>, increased new neuron complexity, and reduced myelination. Interestingly, multiple genes critical for </span></span>neurodevelopment and cognitive function exhibit reduced levels in mature but not nascent transcripts. We infer that the entire Top3b-Tdrd3 complex is essential for normal brain function, and that defective post-transcriptional regulation could contribute to cognitive and psychiatric disorders.</span></p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"233 ","pages":"Article 102568"},"PeriodicalIF":6.7000,"publicationDate":"2024-01-10","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/S0301008224000042","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

Abstract

The Topoisomerase 3B (Top3b) - Tudor domain containing 3 (Tdrd3) protein complex is the only dual-activity topoisomerase complex that can alter both DNA and RNA topology in animals. TOP3B mutations in humans are associated with schizophrenia, autism and cognitive disorders; and Top3b-null mice exhibit several phenotypes observed in animal models of psychiatric and cognitive disorders, including impaired cognitive and emotional behaviors, aberrant neurogenesis and synaptic plasticity, and transcriptional defects. Similarly, human TDRD3 genomic variants have been associated with schizophrenia, verbal short-term memory and educational attainment. However, the importance of Tdrd3 in normal brain function has not been examined in animal models. Here we generated a Tdrd3-null mouse strain and demonstrate that these mice display both shared and unique defects when compared to Top3b-null mice. Shared defects were observed in cognitive behaviors, synaptic plasticity, adult neurogenesis, newborn neuron morphology, and neuronal activity-dependent transcription; whereas defects unique to Tdrd3-deficient mice include hyperactivity, changes in anxiety-like behaviors, olfaction, increased new neuron complexity, and reduced myelination. Interestingly, multiple genes critical for neurodevelopment and cognitive function exhibit reduced levels in mature but not nascent transcripts. We infer that the entire Top3b-Tdrd3 complex is essential for normal brain function, and that defective post-transcriptional regulation could contribute to cognitive and psychiatric disorders.

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
Tdrd3缺失小鼠表现出与神经发生和突触可塑性相关的转录后和行为障碍
拓扑异构酶 3B(TOP3B)--含都铎结构域 3(Tdrd3)蛋白复合物是动物体内唯一能改变 DNA 和 RNA 拓扑的双活性拓扑异构酶复合物。人类的 TOP3B 基因突变与精神分裂症、自闭症和认知障碍有关;TOP3b 基因缺失的小鼠表现出在精神和认知障碍动物模型中观察到的几种表型,包括认知和情感行为受损、神经发生和突触可塑性异常以及转录缺陷。同样,人类 TDRD3 基因组变异也与精神分裂症、言语短期记忆和教育程度有关。然而,Tdrd3 在正常大脑功能中的重要性尚未在动物模型中得到研究。在这里,我们产生了一个 Tdrd3 基因缺失小鼠品系,并证明与 Top3b 基因缺失小鼠相比,这些小鼠显示出共同和独特的缺陷。在认知行为、突触可塑性、成神经发生、新生神经元形态和神经元活动依赖性转录等方面观察到了共同的缺陷;而 Tdrd3 缺失小鼠特有的缺陷包括多动、焦虑样行为变化、嗅觉、新生神经元复杂性增加和髓鞘化减少。有趣的是,多个对神经发育和认知功能至关重要的基因表现出成熟转录本水平降低,而非新生转录本水平降低。我们推断,整个 Top3b-Tdrd3 复合物对正常的大脑功能至关重要,转录后调控缺陷可能导致认知和精神疾病。
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
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
Receptor-dependent influence of R7 RGS proteins on neuronal GIRK channel signaling dynamics CB1 receptors in NG2 cells mediate cannabinoid-evoked functional myelin regeneration 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 Cerebellar impairments in genetic models of autism spectrum disorders: A neurobiological perspective
×
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