[논문]Early correction of synaptic long-term depression improves abnormal anxiety-like behavior in adult GluN2B-C456Y-mutant mice

Shin, Wangyong; Kim, Kyungdeok; Serraz, Benjamin; Cho, Yi Sul; Kim, Doyoun; Kang, Muwon; Lee, Eun-Jae; Lee, Hyejin; Bae, Yong Chul; Paoletti, Pierre; Kim, Eunjoon

doi:10.1371/journal.pbio.3000717

[해외논문] Early correction of synaptic long-term depression improves abnormal anxiety-like behavior in adult GluN2B-C456Y-mutant mice 원문보기

PLoS biology, v.18 no.4, 2020년, pp.e3000717 -

Shin, Wangyong (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea) , Kim, Kyungdeok (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea) , Serraz, Benjamin (Institut de Biologie de l'Ecole Normale Supé) , Cho, Yi Sul (rieure (IBENS), Ecole Normale Supé) , Kim, Doyoun (rieure, Université) , Kang, Muwon (PSL, CNRS, INSERM, Paris, France) , Lee, Eun-Jae (Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea) , Lee, Hyejin (Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea) , Bae, Yong Chul (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea) , Paoletti, Pierre (Department of Neurology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea) , Kim, Eunjoon (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea)

Abstract ▼ AI-Helper

Extensive evidence links Glutamate receptor, ionotropic, NMDA2B (GRIN2B), encoding the GluN2B/NR2B subunit of N-methyl-D-aspartate receptors (NMDARs), with various neurodevelopmental disorders, including autism spectrum disorders (ASDs), but the underlying mechanisms remain unclear. In addition, it remains unknown whether mutations in GluN2B, which starts to be expressed early in development, induces early pathophysiology that can be corrected by early treatments for long-lasting effects. We generated and characterized Grin2b-mutant mice that carry a heterozygous, ASD-risk C456Y mutation (Grin2b+/C456Y). In Grin2b+/C456Y mice, GluN2B protein levels were strongly reduced in association with decreased hippocampal NMDAR currents and NMDAR-dependent long-term depression (LTD) but unaltered long-term potentiation, indicative of mutation-induced protein degradation and LTD sensitivity. Behaviorally, Grin2b+/C456Y mice showed normal social interaction but exhibited abnormal anxiolytic-like behavior. Importantly, early, but not late, treatment of young Grin2b+/C456Y mice with the NMDAR agonist D-cycloserine rescued NMDAR currents and LTD in juvenile mice and improved anxiolytic-like behavior in adult mice. Therefore, GluN2B-C456Y haploinsufficiency decreases GluN2B protein levels, NMDAR-dependent LTD, and anxiety-like behavior, and early activation of NMDAR function has long-lasting effects on adult mouse behavior.Mice that carry a heterozygous, autism spectrum disorder-risk C456Y mutation in the NMDA receptor (NMDAR) subunit GluN2B show decreased protein levels, hippocampal NMDAR currents, and NMDAR-dependent long-term depression and have abnormal anxiolytic-like behavior. Early, but not late, treatment of the young mice with the NMDAR agonist D-cycloserine rescues these phenotypes.

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표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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