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Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits

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Title
Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits
Author(s)
Heejin Cho; Taesun Yoo; Moon, Heera; Kang, Hyojin; Yang, Yeji; Kang, MinSoung; Yang, Esther; Lee, Dowoon; Hwang, Daehee; Kim, Hyun; Kim, Doyoun; Kim, Jin Young; Eunjoon Kim
Publication Date
2023-08
Journal
Molecular Psychiatry, v.28, no.8, pp.3548 - 3562
Publisher
Springer Nature
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. © 2023, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/14135
DOI
10.1038/s41380-023-02129-5
ISSN
1359-4184
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > 1. Journal Papers (저널논문)
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