한빛사논문
- 조회364
Heejin Cho 1,2,9, Taesun Yoo 2,9, Heera Moon 1, Hyojin Kang 3, Yeji Yang 1,4, MinSoung Kang 5, Esther Yang 6, Dowoon Lee 7, Daehee Hwang 7, Hyun Kim 6, Doyoun Kim 5,8, Jin Young Kim 4 and Eunjoon Kim 1,2,*
1Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 34141, Korea.
2Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 34141, Korea.
3Division of National Supercomputing, Korea Institute of Science and Technology Information, Daejeon 34141, Korea.
4Research Center for Bioconvergence Analysis, Korea Basic Science Institute, 162 Yeongudanjiro, Ochang, Cheongju, Chungbuk 28119, Korea.
5Therapeutics & Biotechnology Division, Drug discovery platform research center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea.
6Department of Anatomy and BK21 Graduate Program, Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.
7School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
8Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), Daejeon 34113, Korea.
9These authors contributed equally: Heejin Cho, Taesun Yoo.
*Corresponding author: correspondence to Eunjoon Kim
Abstract
ADNP syndrome, involving the ADNP transcription factor of the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these mice display abnormal synaptic functions remain poorly understood. Here, we report synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIα hyperactivity in Adnp-HT mice. These mice show impaired and inflexible contextual learning and memory, additional to social deficits, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. The adult Adnp-HT hippocampus shows hyperphosphorylated CaMKIIα and its substrates, including SynGAP1, and excessive long-term potentiation that is normalized by CaMKIIα inhibition. Therefore, Adnp haploinsufficiency in mice leads to cognitive inflexibility involving CaMKIIα hyperphosphorylation and excessive LTP in adults long after its marked expressional decrease in juveniles.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-29)
- 국내 연구진
- 생명과학 > 생리학
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