DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yoo, Ye-Eun | ko |
dc.contributor.author | Lee, Seungjoon | ko |
dc.contributor.author | Kim, Woohyun | ko |
dc.contributor.author | Kim, Hyosang | ko |
dc.contributor.author | Chung, Changuk | ko |
dc.contributor.author | Ha, Seungmin | ko |
dc.contributor.author | Park, Jinsu | ko |
dc.contributor.author | Chung, Yeonseung | ko |
dc.contributor.author | Kang, Hyojin | ko |
dc.contributor.author | Kim, Eunjoon | ko |
dc.date.accessioned | 2021-10-11T05:11:04Z | - |
dc.date.available | 2021-10-11T05:11:04Z | - |
dc.date.created | 2021-10-11 | - |
dc.date.created | 2021-10-11 | - |
dc.date.created | 2021-10-11 | - |
dc.date.issued | 2021-09 | - |
dc.identifier.citation | FRONTIERS IN MOLECULAR NEUROSCIENCE, v.14 | - |
dc.identifier.issn | 1662-5099 | - |
dc.identifier.uri | http://hdl.handle.net/10203/288136 | - |
dc.description.abstract | 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 [similar to postnatal day (P21)] and adult (>P56) stages that are rescued by NMDAR activation. However, at similar to 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 (similar to 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.</p> | - |
dc.language | English | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.title | Early Chronic Memantine Treatment-Induced Transcriptomic Changes in Wild-Type and Shank2-Mutant Mice | - |
dc.type | Article | - |
dc.identifier.wosid | 000701289000001 | - |
dc.identifier.scopusid | 2-s2.0-85116014964 | - |
dc.type.rims | ART | - |
dc.citation.volume | 14 | - |
dc.citation.publicationname | FRONTIERS IN MOLECULAR NEUROSCIENCE | - |
dc.identifier.doi | 10.3389/fnmol.2021.712576 | - |
dc.contributor.localauthor | Chung, Yeonseung | - |
dc.contributor.localauthor | Kim, Eunjoon | - |
dc.contributor.nonIdAuthor | Chung, Changuk | - |
dc.contributor.nonIdAuthor | Ha, Seungmin | - |
dc.contributor.nonIdAuthor | Kang, Hyojin | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | autism spectrum disorders | - |
dc.subject.keywordAuthor | Shank2 | - |
dc.subject.keywordAuthor | NMDA receptor | - |
dc.subject.keywordAuthor | memantine | - |
dc.subject.keywordAuthor | RNA-Seq | - |
dc.subject.keywordAuthor | synapse | - |
dc.subject.keywordAuthor | ribosome | - |
dc.subject.keywordAuthor | mitochondria | - |
dc.subject.keywordPlus | AUTISM SPECTRUM DISORDER | - |
dc.subject.keywordPlus | SET ENRICHMENT ANALYSIS | - |
dc.subject.keywordPlus | RARE SHANK2 VARIANTS | - |
dc.subject.keywordPlus | POSTSYNAPTIC DENSITY | - |
dc.subject.keywordPlus | BINDING-PROTEIN | - |
dc.subject.keywordPlus | EMERGING ROLE | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | GENES | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | FAMILY | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.