Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.

IF 4.3 2区 生物学 Q1 BIOLOGY Biological Research Pub Date : 2024-06-18 DOI:10.1186/s40659-024-00522-0
Bastián I Cortés, Rodrigo C Meza, Carlos Ancatén-González, Nicolás M Ardiles, María-Ignacia Aránguiz, Hideaki Tomita, David R Kaplan, Francisca Cornejo, Alexia Nunez-Parra, Pablo R Moya, Andrés E Chávez, Gonzalo I Cancino
{"title":"Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.","authors":"Bastián I Cortés, Rodrigo C Meza, Carlos Ancatén-González, Nicolás M Ardiles, María-Ignacia Aránguiz, Hideaki Tomita, David R Kaplan, Francisca Cornejo, Alexia Nunez-Parra, Pablo R Moya, Andrés E Chávez, Gonzalo I Cancino","doi":"10.1186/s40659-024-00522-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown.</p><p><strong>Results: </strong>Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety.</p><p><strong>Conclusions: </strong>These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"40"},"PeriodicalIF":4.3000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186208/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s40659-024-00522-0","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown.

Results: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety.

Conclusions: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.

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
蛋白酪氨酸磷酸酶受体δ PTPRD的缺失会增加成年小鼠大脑皮层神经元的数量、损害突触功能并诱发类似自闭症的行为。
背景:大脑皮层负责许多高级认知功能。大脑皮层发育过程中的干扰会对大脑功能产生长期影响,并与脑部疾病的病因有关。我们之前发现,蛋白酪氨酸磷酸酶受体δ Ptprd 是大脑皮层发育的关键,它与几种人类神经发育障碍有遗传关联。Ptprd 的表达缺失会过度激活神经前体细胞中的促神经再生受体 TrkB 和 PDGFRβ,从而诱发胚胎和新生小鼠兴奋性神经元的异常增加。然而,这些改变是否会对成年期产生长期影响仍是未知数:结果:在这里,我们发现在 Ptprd+/- 或 Ptprd-/- 小鼠中,兴奋性神经元的发育增加会持续到成年,从而影响内侧前额叶皮层的兴奋性突触功能。同样,Ptprd 的杂合性或同源性也会诱导抑制性皮质 GABA 能神经元的增加,并损害抑制性突触传递。最后,Ptprd+/- 或 Ptprd-/- 小鼠表现出类似自闭症的行为,但没有学习和记忆障碍或焦虑:这些结果表明,Ptprd 的缺失会对大脑皮层神经元数量和突触功能产生长期影响,并可能对类似 ASD 的行为产生异常影响。
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
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
期刊最新文献
Effect of chronic exogenous oxytocin administration on exercise performance and cardiovagal control in hypobaric hypoxia in rats. Depression like-behavior and memory loss induced by methylglyoxal is associated with tryptophan depletion and oxidative stress: a new in vivo model of neurodegeneration. Overexpression of autophagy enhancer PACER/RUBCNL in neurons accelerates disease in the SOD1G93A ALS mouse model. Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12. Impact of salmon farming in the antibiotic resistance and structure of marine bacterial communities from surface seawater of a northern Patagonian area of Chile.
×
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