Yang XY, Ma ZL, Storm DR, Cao H, Zhang YQ. Selective ablation of type 3 adenylyl cyclase in somatostatin-positive interneurons produces anxiety- and depression-like behaviors in mice. World J Psychiatr 2021; 11(2): 35-49 [PMID: 33643860 DOI: 10.5498/wjp.v11.i2.35]
Corresponding Author of This Article
Hong Cao, MD, PhD, Associate Professor, Department of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Institutes of Integrative Medicine, Fudan University, Rm 1202 Mingdao Building, No. 131 Dong'an Road, Shanghai 200032, China. hongcao@fudan.edu.cn
Research Domain of This Article
Psychiatry
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Psychiatr. Feb 19, 2021; 11(2): 35-49 Published online Feb 19, 2021. doi: 10.5498/wjp.v11.i2.35
Selective ablation of type 3 adenylyl cyclase in somatostatin-positive interneurons produces anxiety- and depression-like behaviors in mice
Xiao-Yu Yang, Zhao-Liang Ma, Daniel R Storm, Hong Cao, Yu-Qiu Zhang
Xiao-Yu Yang, Zhao-Liang Ma, Hong Cao, Yu-Qiu Zhang, Department of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Institutes of Integrative Medicine, Fudan University, Shanghai 200032, China
Daniel R Storm, Department of Pharmacology, University of Washington, Seattle, WA 98105, United States
Author contributions: Yang XY and Cao H designed and coordinated the study; Yang XY and Ma ZL performed the experiments, acquired, and analyzed data; Storm DR provided the Floxed AC3 mice; Cao H and Zhang YQ interpreted the data; Yang XY, Storm DR and Cao H wrote the manuscript; All authors approved the final version of the article.
Supported byNational Natural Science Foundation of China, No. 81771208 and No. 81971043
Institutional animal care and use committee statement: The study was reviewed and approved by the Experimental Animal Ethics Committee of Shanghai Medical College and the Institutional Animal Care & Use Committee (IACUC) of Fudan University (permit No. 20170223-091). All experimental procedures were designed to minimize pain or discomfort to the animals and followed the ethical guidelines of the International Association for the Study of Pain regarding the use of laboratory animal.
Conflict-of-interest statement: All authors have no any conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Cao, MD, PhD, Associate Professor, Department of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Institutes of Integrative Medicine, Fudan University, Rm 1202 Mingdao Building, No. 131 Dong'an Road, Shanghai 200032, China. hongcao@fudan.edu.cn
Received: October 13, 2020 Peer-review started: October 13, 2020 First decision: December 4, 2020 Revised: December 9, 2020 Accepted: December 24, 2020 Article in press: December 24, 2020 Published online: February 19, 2021 Processing time: 104 Days and 22.9 Hours
ARTICLE HIGHLIGHTS
Research background
Major depressive disorder (MDD) is a highly disabling and phenotypically heterogeneous psychiatric syndrome that is among the leading contributors to social and economic burden.
Research motivation
Studies from patients and animal models suggest a key role for functional imbalances between the excitatory and inhibitory neurotransmitters in the central nervous system. Somatostatin-positive (SST+) and parvalbumin-positive (PV+) neurons are two major GABAergic interneurons and play roles in excitation/inhibition balance. Type 3 adenylyl cyclase (AC3) has been reported as a top-ranked gene in MDD and our previous study indicated that AC3 globally knockout mice showed depression-like behaviors. We hope to know whether AC3 in these two subtypes of interneurons contributes to the pathophysiological process of depression.
Research objectives
To determine whether ablation of AC3 gene in different subtypes of GABAergic interneurons of mice produces depression-like behaviors.
Research methods
Immunohistochemistry, genetic manipulations, and a series of behavior tests were used in this study.
Research results
We found that selective disruption of AC3 in SST+ but not PV+ interneurons caused anxiety- and depression-like behaviors.
Research conclusions
AC3 in SST+ interneurons play a key role in the etiology of depression.
Research perspectives
The AC3-dependent molecular mechanisms in SST+ interneuron underlying MDD will be further explored.
