DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Seung-Hyun | ko |
dc.contributor.author | Zhang, Yinhua | ko |
dc.contributor.author | Park, Jina | ko |
dc.contributor.author | Kim, Bowon | ko |
dc.contributor.author | Kim, Yangsik | ko |
dc.contributor.author | Lee, Sang Hoon | ko |
dc.contributor.author | Kim, Gyu Hyun | ko |
dc.contributor.author | Huh, Yang Hoon | ko |
dc.contributor.author | Lee, Bokyoung | ko |
dc.contributor.author | Kim, Yoonhee | ko |
dc.contributor.author | Lee, Yeunkum | ko |
dc.contributor.author | Kim, Jin Yong | ko |
dc.contributor.author | Kang, Hyojin | ko |
dc.contributor.author | Choi, Su-Yeon | ko |
dc.contributor.author | Jang, Seil | ko |
dc.contributor.author | Li, Yan | ko |
dc.contributor.author | Kim, Shinhyun | ko |
dc.contributor.author | Jin, Chunmei | ko |
dc.contributor.author | Pang, Kaifang | ko |
dc.contributor.author | Kim, Eunjeong | ko |
dc.contributor.author | Lee, Yoontae | ko |
dc.contributor.author | Kim, Hyun | ko |
dc.contributor.author | Kim, Eunjoon | ko |
dc.contributor.author | Choi, Jee Hyun | ko |
dc.contributor.author | Kim, Jeongjin | ko |
dc.contributor.author | Lee, Kea Joo | ko |
dc.contributor.author | Choi, Se-Young | ko |
dc.contributor.author | Han, Kihoon | ko |
dc.date.accessioned | 2021-03-26T02:15:51Z | - |
dc.date.available | 2021-03-26T02:15:51Z | - |
dc.date.created | 2020-08-10 | - |
dc.date.issued | 2020-09 | - |
dc.identifier.citation | ANNALS OF NEUROLOGY, v.88, no.3, pp.526 - 543 | - |
dc.identifier.issn | 0364-5134 | - |
dc.identifier.uri | http://hdl.handle.net/10203/281913 | - |
dc.description.abstract | Objective Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments forCYFIP2-associated brain disorders remain largely unknown. Here, we characterizedCyfip2heterozygous (Cyfip2(+/-)) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of theCyfip2(+/-)mice and specified a neuronal function mediating its efficacy. Methods We performed behavioral analyses ofCyfip2(+/-)mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses ofCyfip2(+/-)prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections. Results AdultCyfip2(+/-)mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adultCyfip2(+/-)PFC that was restricted to layer 5 (L5) neurons. Consistently, adultCyfip2(+/-)mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability ofCyfip2(+/-)L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adultCyfip2(+/-)PFC. Virus-mediated reduction of CYFIP2 in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior. Interpretation These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and the lithium-mediated amelioration of neurobehavioral phenotypes in adultCyfip2(+/-)mice, which can be implicated inCYFIP2-associated brain disorders. | - |
dc.language | English | - |
dc.publisher | WILEY | - |
dc.title | Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction | - |
dc.type | Article | - |
dc.identifier.wosid | 000552494700001 | - |
dc.identifier.scopusid | 2-s2.0-85088588741 | - |
dc.type.rims | ART | - |
dc.citation.volume | 88 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 526 | - |
dc.citation.endingpage | 543 | - |
dc.citation.publicationname | ANNALS OF NEUROLOGY | - |
dc.identifier.doi | 10.1002/ana.25827 | - |
dc.contributor.localauthor | Kim, Eunjoon | - |
dc.contributor.nonIdAuthor | Lee, Seung-Hyun | - |
dc.contributor.nonIdAuthor | Zhang, Yinhua | - |
dc.contributor.nonIdAuthor | Park, Jina | - |
dc.contributor.nonIdAuthor | Kim, Bowon | - |
dc.contributor.nonIdAuthor | Lee, Sang Hoon | - |
dc.contributor.nonIdAuthor | Kim, Gyu Hyun | - |
dc.contributor.nonIdAuthor | Huh, Yang Hoon | - |
dc.contributor.nonIdAuthor | Lee, Bokyoung | - |
dc.contributor.nonIdAuthor | Kim, Yoonhee | - |
dc.contributor.nonIdAuthor | Lee, Yeunkum | - |
dc.contributor.nonIdAuthor | Kim, Jin Yong | - |
dc.contributor.nonIdAuthor | Kang, Hyojin | - |
dc.contributor.nonIdAuthor | Kim, Shinhyun | - |
dc.contributor.nonIdAuthor | Jin, Chunmei | - |
dc.contributor.nonIdAuthor | Pang, Kaifang | - |
dc.contributor.nonIdAuthor | Kim, Eunjeong | - |
dc.contributor.nonIdAuthor | Lee, Yoontae | - |
dc.contributor.nonIdAuthor | Kim, Hyun | - |
dc.contributor.nonIdAuthor | Choi, Jee Hyun | - |
dc.contributor.nonIdAuthor | Kim, Jeongjin | - |
dc.contributor.nonIdAuthor | Lee, Kea Joo | - |
dc.contributor.nonIdAuthor | Choi, Se-Young | - |
dc.contributor.nonIdAuthor | Han, Kihoon | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | DENDRITIC SPINES | - |
dc.subject.keywordPlus | LITHIUM | - |
dc.subject.keywordPlus | OSCILLATIONS | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | CHANNELS | - |
dc.subject.keywordPlus | INSIGHTS | - |
dc.subject.keywordPlus | BEHAVIOR | - |
dc.subject.keywordPlus | DELETION | - |
dc.subject.keywordPlus | DENSITY | - |
dc.subject.keywordPlus | NETWORK | - |
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