Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Lee, Seung-Hyun | - |
dc.contributor.author | Zhang, Yinhua | - |
dc.contributor.author | Park, Jina | - |
dc.contributor.author | Kim, Bowon | - |
dc.contributor.author | Kim, Yangsik | - |
dc.contributor.author | Lee, Sang Hoon | - |
dc.contributor.author | Kim, Gyu Hyun | - |
dc.contributor.author | Huh, Yang Hoon | - |
dc.contributor.author | Lee, Bokyoung | - |
dc.contributor.author | Kim, Yoonhee | - |
dc.contributor.author | Lee, Yeunkum | - |
dc.contributor.author | Kim, Jin Yong | - |
dc.contributor.author | Kang, Hyojin | - |
dc.contributor.author | Choi, Su-Yeon | - |
dc.contributor.author | Jang, Seil | - |
dc.contributor.author | Li, Yan | - |
dc.contributor.author | Kim, Shinhyun | - |
dc.contributor.author | Jin, Chunmei | - |
dc.contributor.author | Pang, Kaifang | - |
dc.contributor.author | Kim, Eunjeong | - |
dc.contributor.author | Lee, Yoontae | - |
dc.contributor.author | Kim, Hyun | - |
dc.contributor.author | Kim, Eunjoon | - |
dc.contributor.author | Choi, Jee Hyun | - |
dc.contributor.author | Kim, Jeongjin | - |
dc.contributor.author | Lee, Kea Joo | - |
dc.contributor.author | Choi, Se-Young | - |
dc.contributor.author | Han, Kihoon | - |
dc.date.accessioned | 2021-01-22T07:34:00Z | - |
dc.date.available | 2021-01-22T07:34:00Z | - |
dc.date.created | 2020-07-02 | - |
dc.date.issued | 2020-09 | - |
dc.identifier.issn | 0364-5134 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/12799 | - |
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 for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/−) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/− mice and specified a neuronal function mediating its efficacy. Methods: We performed behavioral analyses of Cyfip2+/− mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses of Cyfip2+/− prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections. Results: Adult Cyfip2+/− mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2+/− PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2+/− 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 of Cyfip2+/− L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2+/− 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 adult Cyfip2+/− mice, which can be implicated in CYFIP2-associated brain disorders. ANN NEUROL 2020;88:526–543. © 2020 American Neurological Association | - |
dc.language | English | - |
dc.publisher | John Wiley & Sons Inc. | - |
dc.title | Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction | - |
dc.type | Article | - |
dc.identifier.doi | 10.1002/ana.25827 | - |
dc.identifier.wosid | 000552494700001 | - |
dc.identifier.scopusid | 2-s2.0-85088588741 | - |
dc.identifier.bibliographicCitation | Annals of Neurology, v.88, no.3, pp.526 - 543 | - |
dc.description.isOpenAccess | FALSE | - |
dc.subject.keywordPlus | DENDRITIC SPINES | - |
dc.subject.keywordPlus | OSCILLATIONS | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | CHANNELS | - |
dc.subject.keywordPlus | INSIGHTS | - |
dc.subject.keywordPlus | AUTISM | - |
dc.subject.keywordPlus | BEHAVIOR | - |
dc.subject.keywordPlus | DELETION | - |
dc.subject.keywordPlus | DENSITY | - |
dc.subject.keywordPlus | NETWORK | - |
dc.citation.endPage | 543 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 526 | - |
dc.citation.title | Annals of Neurology | - |
dc.citation.volume | 88 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Clinical Neurology; Neurosciences | - |
dc.type.docType | Article | - |
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