Upregulation of carbonic anhydrase 1 beneficial for depressive disorder
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01545-6 |
| _version_ | 1797849822622908416 |
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| author | Ke Cheng Yue Wang Yong He Yu Tian Junjie Li Chong Chen Xingzhe Xu Zhonghao Wu Heming Yu Xiangyu Chen Yili Wu Weihong Song Zhifang Dong Huatai Xu Peng Xie |
| author_facet | Ke Cheng Yue Wang Yong He Yu Tian Junjie Li Chong Chen Xingzhe Xu Zhonghao Wu Heming Yu Xiangyu Chen Yili Wu Weihong Song Zhifang Dong Huatai Xu Peng Xie |
| author_sort | Ke Cheng |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T18:50:24Z |
| format | Article |
| id | doaj.art-40779fbd53c7457dadf7693a13944c94 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-09T18:50:24Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-40779fbd53c7457dadf7693a13944c942023-04-09T11:29:28ZengBMCActa Neuropathologica Communications2051-59602023-04-0111111410.1186/s40478-023-01545-6Upregulation of carbonic anhydrase 1 beneficial for depressive disorderKe Cheng0Yue Wang1Yong He2Yu Tian3Junjie Li4Chong Chen5Xingzhe Xu6Zhonghao Wu7Heming Yu8Xiangyu Chen9Yili Wu10Weihong Song11Zhifang Dong12Huatai Xu13Peng Xie14NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityMinistry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and DisordersNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Zhejiang Provincial Clinical Research Center for Mental Disorders, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, School of Mental Health and Kangning Hospital, Wenzhou Medical UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Zhejiang Provincial Clinical Research Center for Mental Disorders, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, School of Mental Health and Kangning Hospital, Wenzhou Medical UniversityMinistry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and DisordersInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityAbstract 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.https://doi.org/10.1186/s40478-023-01545-6Carbonic anhydrase 1Hippocampal astrocytesMiniature inhibitory postsynaptic currentsCAR1-knockout miceMajor depressive disorder |
| spellingShingle | Ke Cheng Yue Wang Yong He Yu Tian Junjie Li Chong Chen Xingzhe Xu Zhonghao Wu Heming Yu Xiangyu Chen Yili Wu Weihong Song Zhifang Dong Huatai Xu Peng Xie Upregulation of carbonic anhydrase 1 beneficial for depressive disorder Acta Neuropathologica Communications Carbonic anhydrase 1 Hippocampal astrocytes Miniature inhibitory postsynaptic currents CAR1-knockout mice Major depressive disorder |
| title | Upregulation of carbonic anhydrase 1 beneficial for depressive disorder |
| title_full | Upregulation of carbonic anhydrase 1 beneficial for depressive disorder |
| title_fullStr | Upregulation of carbonic anhydrase 1 beneficial for depressive disorder |
| title_full_unstemmed | Upregulation of carbonic anhydrase 1 beneficial for depressive disorder |
| title_short | Upregulation of carbonic anhydrase 1 beneficial for depressive disorder |
| title_sort | upregulation of carbonic anhydrase 1 beneficial for depressive disorder |
| topic | Carbonic anhydrase 1 Hippocampal astrocytes Miniature inhibitory postsynaptic currents CAR1-knockout mice Major depressive disorder |
| url | https://doi.org/10.1186/s40478-023-01545-6 |
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