Upregulation of carbonic anhydrase 1 beneficial for depressive disorder

作者全名："Cheng, Ke; Wang, Yue; He, Yong; Tian, Yu; Li, Junjie; Chen, Chong; Xu, Xingzhe; Wu, Zhonghao; Yu, Heming; Chen, Xiangyu; Wu, Yili; Song, Weihong; Dong, Zhifang; Xu, Huatai; Xie, Peng"

作者地址："[Cheng, Ke; Wang, Yue; He, Yong; Tian, Yu; Chen, Chong; Xu, Xingzhe; Wu, Zhonghao; Xie, Peng] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Cheng, Ke; Wang, Yue; Xu, Huatai] Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Neurosci, Shanghai 200031, Peoples R China; [He, Yong; Tian, Yu; Yu, Heming; Chen, Xiangyu; Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Li, Junjie; Dong, Zhifang] Natl Clin Res Ctr Child Hlth & Disorders, Key Lab Child Dev & Disorders, Minist Educ, Chongqing 400014, Peoples R China; [Li, Junjie; Dong, Zhifang] Chongqing Med Univ, Chongqing Key Lab Translat Med Res Cognit Dev & Le, Childrens Hosp, Chongqing 400014, Peoples R China; [Wu, Yili; Song, Weihong] Wenzhou Med Univ, Inst Aging, Zhejiang Prov Clin Res Ctr Mental Disorders, Sch Mental Hlth,Key Lab Alzheimers Dis Zhejiang Pr, Wenzhou 325000, Zhejiang, Peoples R China; [Wu, Yili; Song, Weihong] Wenzhou Med Univ, Kangning Hosp, Wenzhou 325000, Zhejiang, Peoples R China; [Xu, Huatai] Shanghai Ctr Brain Sci & Brain Inspired Intelligen, Shanghai 201210, Peoples R China"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Xu, HT (通讯作者)，Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Neurosci, Shanghai 200031, Peoples R China.; Xie, P (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Dong, ZF (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Key Lab Child Dev & Disorders, Minist Educ, Chongqing 400014, Peoples R China.; Dong, ZF (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Translat Med Res Cognit Dev & Le, Childrens Hosp, Chongqing 400014, Peoples R China.; Song, WH (通讯作者)，Wenzhou Med Univ, Inst Aging, Zhejiang Prov Clin Res Ctr Mental Disorders, Sch Mental Hlth,Key Lab Alzheimers Dis Zhejiang Pr, Wenzhou 325000, Zhejiang, Peoples R China.; Song, WH (通讯作者)，Wenzhou Med Univ, Kangning Hosp, Wenzhou 325000, Zhejiang, Peoples R China.; Xu, HT (通讯作者)，Shanghai Ctr Brain Sci & Brain Inspired Intelligen, Shanghai 201210, Peoples R China."

来源：ACTA NEUROPATHOLOGICA COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000964287800001

JCR分区：Q1

影响因子：6.2

年份：2023

卷号：11

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Carbonic anhydrase 1; Hippocampal astrocytes; Miniature inhibitory postsynaptic currents; CAR1-knockout mice; Major depressive disorder

摘要："Carbonic Anhydrase 1 (CAR1) is a zinc-metalloenzyme that catalyzes the hydration of carbon dioxide, and the alteration of CAR1 has been implicated in neuropsychiatric disorders. However, the mechanism underlying the role of CAR1 in major depressive disorder (MDD) remains largely unknown. In this study, we report the decreased level of CAR1 in MDD patients and depression-like model rodents. We found that CAR1 is expressed in hippocampal astrocytes and CAR1 regulates extracellular bicarbonate concentration and pH value in the partial hilus. Ablation of the CAR1 gene increased the activity of granule cells via decreasing their miniature inhibitory postsynaptic currents (mIPSC), and caused depression-like behaviors in CAR1-knockout mice. Astrocytic CAR1 expression rescued the deficits in mIPSCs of granule cells and reduced depression-like behaviors in CAR1 deficient mice. Furthermore, pharmacological activation of CAR1 and overexpression of CAR1 in the ventral hippocampus of mice improved depressive behaviors. These findings uncover a critical role of CAR1 in the MDD pathogenesis and its therapeutic potential."

基金机构："National Key R&D Program of China [2017YFA0505703, 81901398]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; National Key Program International Cooperation Project [81820108015]; National Natural Science Foundation of China [31671113, 2017YFA0505700, 81701361]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB32010100]; Shanghai Municipal Science and Technology Major Project [2018SHZDZX05]; State Key Laboratory of Neuroscience; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0213]"

基金资助正文："We thank Prof. Tifei Yuan for providing the whole-cell recording platform; other members in Xu lab for their discussions and technique supports. The work was supported by the National Key R & D Program of China (2017YFA0505700), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT320002), the National Key Program International Cooperation Project (No. 81820108015), and the National Natural Science Foundation of China (No. 81701361 and No. 81901398); National Key R & D Program of China, grant No. 2017YFA0505703; Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB32010100); National Natural Science Foundation of China (project 31671113); Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX05)and the support from the State Key Laboratory of Neuroscience; Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0213)."