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YOOK, Chaehyun
시냅스 뇌질환 연구단
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Adult re-expression of IRSp53 rescues NMDA receptor function and social behavior in IRSp53-mutant mice

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Title
Adult re-expression of IRSp53 rescues NMDA receptor function and social behavior in IRSp53-mutant mice
Author(s)
Noh, Young Woo; Chaehyun Yook; Jaeseung Kang; Lee, Soowon; Kim, Yeonghyeon; Yang, Esther; Kim, Hyun; Eunjoon Kim
Publication Date
2022-08
Journal
COMMUNICATIONS BIOLOGY, v.5, no.1
Publisher
NATURE PORTFOLIO
Abstract
Re-expression of the insulin receptor substrate p53 (IRSp53) in adult IRSp53-mutant mice rescues behavioral and synaptic deficits, suggesting that adult re-expression may hold future therapeutic potential. IRSp53 (or BAIAP2) is an abundant excitatory postsynaptic scaffolding/adaptor protein that is involved in actin regulation and has been implicated in autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. IRSp53 deletion in mice leads to enhanced NMDA receptor (NMDAR) function and social deficits that are responsive to NMDAR inhibition. However, it remains unclear whether IRSp53 re-expression in the adult IRSp53-mutant mouse brain after the completion of brain development could reverse these synaptic and behavioral dysfunctions. Here we employed a brain-blood barrier (BBB)-penetrant adeno-associated virus (AAV) known as PHP.eB to drive adult IRSp53 re-expression in IRSp53-mutant mice. The adult IRSp53 re-expression normalized social deficits without affecting hyperactivity or anxiety-like behavior. In addition, adult IRSp53 re-expression normalized NMDAR-mediated excitatory synaptic transmission in the medial prefrontal cortex. Our results suggest that adult IRSp53 re-expression can normalize synaptic and behavioral deficits in IRSp53-mutant mice and that BBB-penetrant adult gene re-expression has therapeutic potential.
URI
https://pr.ibs.re.kr/handle/8788114/12346
DOI
10.1038/s42003-022-03813-y
ISSN
2399-3642
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > 1. Journal Papers (저널논문)
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