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시냅스뇌질환연구단
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Early Chronic Memantine Treatment-Induced Transcriptomic Changes in Wild-Type and Shank2-Mutant Mice

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dc.contributor.authorYe-Eun Yoo-
dc.contributor.authorLee, Seungjoon-
dc.contributor.authorKim, Woohyun-
dc.contributor.authorKim, Hyosang-
dc.contributor.authorChanguk Chung-
dc.contributor.authorSeungmin Ha-
dc.contributor.authorPark, Jinsu-
dc.contributor.authorChung, Yeonseung-
dc.contributor.authorKang, Hyojin-
dc.contributor.authorEunjoon Kim-
dc.date.accessioned2021-11-09T07:30:15Z-
dc.date.available2021-11-09T07:30:15Z-
dc.date.created2021-11-01-
dc.date.issued2021-09-14-
dc.identifier.issn1662-5099-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/10617-
dc.description.abstract© Copyright © 2021 Yoo, Lee, Kim, Kim, Chung, Ha, Park, Chung, Kang and Kim.Shank2 is an excitatory postsynaptic scaffolding protein strongly implicated in autism spectrum disorders (ASDs). Shank2-mutant mice with a homozygous deletion of exons 6 and 7 (Shank2-KO mice) show decreased NMDA receptor (NMDAR) function and autistic-like behaviors at juvenile [∼postnatal day (P21)] and adult (>P56) stages that are rescued by NMDAR activation. However, at ∼P14, these mice show the opposite change – increased NMDAR function; moreover, suppression of NMDAR activity with early, chronic memantine treatment during P7–21 prevents NMDAR hypofunction and autistic-like behaviors at later (∼P21 and >P56) stages. To better understand the mechanisms underlying this rescue, we performed RNA-Seq gene-set enrichment analysis of forebrain transcriptomes from wild-type (WT) and Shank2-KO juvenile (P25) mice treated early and chronically (P7–21) with vehicle or memantine. Vehicle-treated Shank2-KO mice showed upregulation of synapse-related genes and downregulation of ribosome- and mitochondria-related genes compared with vehicle-treated WT mice. They also showed a transcriptomic pattern largely opposite that observed in ASD (reverse-ASD pattern), based on ASD-related/risk genes and cell-type–specific genes. In memantine-treated Shank2-KO mice, chromatin-related genes were upregulated; mitochondria, extracellular matrix (ECM), and actin-related genes were downregulated; and the reverse-ASD pattern was weakened compared with that in vehicle-treated Shank2-KO mice. In WT mice, memantine treatment, which does not alter NMDAR function, upregulated synaptic genes and downregulated ECM genes; memantine-treated WT mice also exhibited a reverse-ASD pattern. Therefore, early chronic treatment of Shank2-KO mice with memantine alters expression of chromatin, mitochondria, ECM, actin, and ASD-related genes.-
dc.language영어-
dc.publisherFrontiers Media S.A.-
dc.titleEarly Chronic Memantine Treatment-Induced Transcriptomic Changes in Wild-Type and Shank2-Mutant Mice-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000701289000001-
dc.identifier.scopusid2-s2.0-85116014964-
dc.identifier.rimsid76565-
dc.contributor.affiliatedAuthorYe-Eun Yoo-
dc.contributor.affiliatedAuthorChanguk Chung-
dc.contributor.affiliatedAuthorSeungmin Ha-
dc.contributor.affiliatedAuthorEunjoon Kim-
dc.identifier.doi10.3389/fnmol.2021.712576-
dc.identifier.bibliographicCitationFrontiers in Molecular Neuroscience, v.14-
dc.relation.isPartOfFrontiers in Molecular Neuroscience-
dc.citation.titleFrontiers in Molecular Neuroscience-
dc.citation.volume14-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaNeurosciences & Neurology-
dc.relation.journalWebOfScienceCategoryNeurosciences-
dc.subject.keywordPlusAUTISM SPECTRUM DISORDER-
dc.subject.keywordPlusSET ENRICHMENT ANALYSIS-
dc.subject.keywordPlusRARE SHANK2 VARIANTS-
dc.subject.keywordPlusPOSTSYNAPTIC DENSITY-
dc.subject.keywordPlusBINDING-PROTEIN-
dc.subject.keywordPlusEMERGING ROLE-
dc.subject.keywordPlusMUTATIONS-
dc.subject.keywordPlusGENES-
dc.subject.keywordPlusBRAIN-
dc.subject.keywordPlusFAMILY-
dc.subject.keywordAuthorautism spectrum disorders-
dc.subject.keywordAuthormemantine-
dc.subject.keywordAuthormitochondria-
dc.subject.keywordAuthorNMDA receptor-
dc.subject.keywordAuthorribosome-
dc.subject.keywordAuthorRNA-Seq-
dc.subject.keywordAuthorShank2-
dc.subject.keywordAuthorsynapse-
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > 1. Journal Papers (저널논문)
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