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DC Field | Value | Language |
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dc.citation.endPage | 265 | - |
dc.citation.number | 7402 | - |
dc.citation.startPage | 261 | - |
dc.citation.title | NATURE | - |
dc.citation.volume | 486 | - |
dc.contributor.author | Won, Hyejung | - |
dc.contributor.author | Lee, Hye-Ryeon | - |
dc.contributor.author | Gee, Heon Yung | - |
dc.contributor.author | Mah, Won | - |
dc.contributor.author | Kim, Jae-Ick | - |
dc.contributor.author | Lee, Jiseok | - |
dc.contributor.author | Ha, Seungmin | - |
dc.contributor.author | Chung, Changuk | - |
dc.contributor.author | Jung, Eun Suk | - |
dc.contributor.author | Cho, Yi Sul | - |
dc.contributor.author | Park, Sae-Geun | - |
dc.contributor.author | Lee, Jung-Soo | - |
dc.contributor.author | Lee, Kyungmin | - |
dc.contributor.author | Kim, Daesoo | - |
dc.contributor.author | Bae, Yong Chul | - |
dc.contributor.author | Kaang, Bong-Kiun | - |
dc.contributor.author | Lee, Min Goo | - |
dc.contributor.author | Kim, Eunjoon | - |
dc.date.accessioned | 2023-12-22T05:07:39Z | - |
dc.date.available | 2023-12-22T05:07:39Z | - |
dc.date.created | 2016-12-08 | - |
dc.date.issued | 2012-06 | - |
dc.description.abstract | Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants(1). Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses(2-4), and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability(5). Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics(6-16), further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation(17), also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD. | - |
dc.identifier.bibliographicCitation | NATURE, v.486, no.7402, pp.261 - 265 | - |
dc.identifier.doi | 10.1038/nature11208 | - |
dc.identifier.issn | 0028-0836 | - |
dc.identifier.scopusid | 2-s2.0-84862297282 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/20966 | - |
dc.identifier.url | http://www.nature.com/nature/journal/v486/n7402/full/nature11208.html | - |
dc.identifier.wosid | 000305189000036 | - |
dc.language | 영어 | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function | - |
dc.type | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | METABOTROPIC GLUTAMATE RECEPTORS | - |
dc.subject.keywordPlus | POSITIVE ALLOSTERIC MODULATOR | - |
dc.subject.keywordPlus | POSTSYNAPTIC DENSITY | - |
dc.subject.keywordPlus | SYNAPTIC PLASTICITY | - |
dc.subject.keywordPlus | SPECTRUM DISORDER | - |
dc.subject.keywordPlus | SHANK3 | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | COMMUNICATION | - |
dc.subject.keywordPlus | TRAFFICKING | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
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