Critical time window and mechanism underlying the development of autistic-like phenotypes in Shank2 knockout mice = Shank2 단백질 결손 생쥐에서의 자폐 유사증상 발현 핵심 시기 및 기전에 대한 연구

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Autism spectrum disorders (ASDs) are neurodevelopmental disorders, which consists of symptoms, such as, social dysfunctions, as well as, repetitive and restricted behaviors. Many animal model studies, which have mimicked genetic mutations in human patients, suggest that synaptic dysfunctions could be a potent underlying mechanism of ASDs. However, it is unknown whether early postnatal developmental processes are involved in later pathogenic changes in the brain. In this study, I show that early correction of a dysregulated synaptic function in young mice prevents manifestation of autistic-like phenotypes in adult mice. Shank2-/- mice, displaying autistic-like behaviors―social dysfunction, repetitive jumping and hyperactivity―and reduced NMDA receptor function at post-weaning stages after postnatal day 21 (>P21), showed earlier NMDA receptor hyperfunction at an pre-weaning age (~P14). Moreover, early suppression of NMDA receptor function (P7-21) by memantine prevented later NMDA receptor hypofunction, social-interaction deficits, and hyperactive locomotion at juvenile and adult stage. Interestingly, mRNA level of oxytocin after early memantine treatment was highly increased in Shank2-/- brain. Acute nasal administration of oxytocin rescued social dysfunction in Shank2-/- mice. These results suggest that specific time-window in which unique synaptic deficits are present and the intervention of NMDA receptor activity at that period could be a potent strategy to prevent autistic-like phenotypes in Shank2-/- mice.
Advisors
Kim, Eunjoonresearcher김은준researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2017
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2017.2,[v, 82 p. :]

Keywords

Autism spectrum disorders▼aTime-window▼aShank2▼aNMDA receptor▼aMemantine; 자폐 스펙트럼 장애▼a중요 시기▼aShank2▼aNMDA 수용체▼a메만틴

URI
http://hdl.handle.net/10203/264775
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=866936&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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