PMID- 37913973
OWN - NLM
STAT- MEDLINE
DCOM- 20240412
LR  - 20240424
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 95
IP  - 9
DP  - 2024 May 1
TI  - Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits 
      by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.
PG  - 896-908
LID - S0006-3223(23)01662-1 [pii]
LID - 10.1016/j.biopsych.2023.10.017 [doi]
AB  - BACKGROUND: Circular RNAs are highly enriched in the synapses of the mammalian 
      brain and play important roles in neurological function by acting as molecular 
      sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 
      gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, 
      the function of circAnk3 remains elusive. In this study, we investigated the 
      function of circAnk3 and its downstream regulatory network for target genes in 
      the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is 
      generated was modified using CRISPR/Cas9 (clustered regularly interspaced short 
      palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and 
      depression-like behaviors, social behaviors) were performed in circAnk3(+/-) 
      mice. A series of molecular and biochemical assays were used to investigate the 
      function of circAnk3 as a microRNA sponge and its downstream regulatory network 
      for target genes. RESULTS: circAnk3(+/-) mice exhibited both anxiety-like 
      behaviors and social deficits. circAnk3 was predominantly located in the 
      cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate 
      the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in 
      the hippocampus ameliorated the behavioral deficits of circAnk3(+/-) mice. 
      Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor 
      subunit GluN2a and impaired the structural plasticity of dendritic synapses in 
      the hippocampus. CONCLUSIONS: Our results reveal an important role of the 
      circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of 
      hippocampal synapses. circAnk3 might offer new insights into the involvement of 
      circular RNAs in neuropsychiatric disorders.
CI  - Copyright (c) 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - He, Yuman
AU  - He Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Jiang, Linhong
AU  - Jiang L
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Liu, Haxiaoyu
AU  - Liu H
AD  - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of 
      Education, Collaborative Innovation Center of Advanced Drug Delivery System and 
      Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, 
      Yantai, China.
FAU - Bu, Qian
AU  - Bu Q
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Kuang, Weihong
AU  - Kuang W
AD  - Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, 
      China.
FAU - Zhao, Ying
AU  - Zhao Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Chen, Yaxing
AU  - Chen Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Zhang, Ni
AU  - Zhang N
AD  - Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, 
      China.
FAU - Xiao, Yuzhou
AU  - Xiao Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Li, Shu
AU  - Li S
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Chen, Rong
AU  - Chen R
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Han, Shuang
AU  - Han S
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Zhou, Yuanyi
AU  - Zhou Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Zhang, Jiamei
AU  - Zhang J
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wan, Xuemei
AU  - Wan X
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Xu, Rui
AU  - Xu R
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Shaomin
AU  - Wang S
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Zhang, Haoluo
AU  - Zhang H
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Gu, Hui
AU  - Gu H
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wei, Qingfan
AU  - Wei Q
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Qin, Feng
AU  - Qin F
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Zhao, Yue
AU  - Zhao Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Li, Hongchun
AU  - Li H
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Liang
AU  - Wang L
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Xiaojie
AU  - Wang X
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Yonghai
AU  - Wang Y
AD  - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of 
      Education, Collaborative Innovation Center of Advanced Drug Delivery System and 
      Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, 
      Yantai, China.
FAU - Dai, Yanping
AU  - Dai Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Li, Min
AU  - Li M
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Chen, Yuanyuan
AU  - Chen Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Hongbo
AU  - Wang H
AD  - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of 
      Education, Collaborative Innovation Center of Advanced Drug Delivery System and 
      Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, 
      Yantai, China.
FAU - Tian, Jingwei
AU  - Tian J
AD  - Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of 
      Education, Collaborative Innovation Center of Advanced Drug Delivery System and 
      Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, 
      Yantai, China.
FAU - Zhao, Yinglan
AU  - Zhao Y
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FAU - Cen, Xiaobo
AU  - Cen X
AD  - Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, 
      State Key Laboratory of Biotherapy and Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, China. Electronic 
      address: xbcen@scu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231030
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (Ank3 protein, mouse)
RN  - 0 (IQ motif containing GTPase activating protein 1)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Anxiety/genetics
MH  - Brain/metabolism
MH  - Hippocampus/metabolism
MH  - Mammals/genetics/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - *RNA, Circular/metabolism
OTO - NOTNLM
OT  - Glutamate receptors
OT  - IQ motif containing GTPase activating protein 1
OT  - Psychiatric disorder
OT  - Synaptic plasticity
OT  - circAnk3
OT  - miR-7080-3p
EDAT- 2023/11/02 00:42
MHDA- 2024/04/12 06:44
CRDT- 2023/11/01 20:29
PHST- 2023/05/11 00:00 [received]
PHST- 2023/10/06 00:00 [revised]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2024/04/12 06:44 [medline]
PHST- 2023/11/02 00:42 [pubmed]
PHST- 2023/11/01 20:29 [entrez]
AID - S0006-3223(23)01662-1 [pii]
AID - 10.1016/j.biopsych.2023.10.017 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2024 May 1;95(9):896-908. doi: 10.1016/j.biopsych.2023.10.017. 
      Epub 2023 Oct 30.