Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice
Background: Astrocytes are essential for synaptic transmission, and their dysfunction can result in neuropsychiatric disorders such as anxiety and depression. Many studies have shown that global knockout of Melatonin receptor 2 (Mtnr1b) is associated with the development of various mental disorders....
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IMR Press
2023-10-01
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| Series: | Journal of Integrative Neuroscience |
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| Online Access: | https://www.imrpress.com/journal/JIN/22/6/10.31083/j.jin2206154 |
| _version_ | 1797365806542094336 |
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| author | Zijun Meng Shipeng Guo Xiangjun Dong Qunxian Wang Dongjie Hu Xiaoqi Liu Yanshuang Jiang Liangye Ji Jie Zhang Weiyi Zhu Weihui Zhou Weihong Song |
| author_facet | Zijun Meng Shipeng Guo Xiangjun Dong Qunxian Wang Dongjie Hu Xiaoqi Liu Yanshuang Jiang Liangye Ji Jie Zhang Weiyi Zhu Weihui Zhou Weihong Song |
| author_sort | Zijun Meng |
| collection | DOAJ |
| description | Background: Astrocytes are essential for synaptic transmission, and their dysfunction can result in neuropsychiatric disorders such as anxiety and depression. Many studies have shown that global knockout of Melatonin receptor 2 (Mtnr1b) is associated with the development of various mental disorders. Aim: This study aimed to investigate the effects of astrocyte ablation of Mtnr1b on cognitive function and anxiety-like behavior in mice, as well as the potential biological mechanisms. Methods: A conditional Cre-loxP system allowing deletion of Mtnr1b from astrocytes was developed to investigate the specific role Mtnr1b. Control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were selected for cognitive function behavioral testing (Morris water maze test, novel object recognition test) and emotion-related behavioral testing (open field, elevated plus maze). After testing, brain tissue was collected and examined by immunofluorescence for the expression of neuronal nuclei (NeuN), glutamate decarboxylase 67 (GAD67), and vesicular glutamate transporter 1 (vGluT1). RNA-seq was performed on hippocampal tissue from control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice to identify differentially expressed genes. Additional confirmation of differential gene expression was performed using real-time quantitative polymerase chain reaction (qRT-PCR). Results: Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were not significantly different from control mice in the Morris water maze and novel object recognition tests. Results from the open field and elevated plus maze tests showed that Mtnr1b cKO𝐺𝑓𝑎𝑝 mice exhibited significantly more anxiety-like behavior than did controls. Immunofluorescence revealed that the number of mature neurons did not differ significantly between Mtnr1b cKO𝐺𝑓𝑎𝑝 mice and controls. The expression of GAD67 in the hippocampal CA1 and CA3 areas of Mtnr1b cKO𝐺𝑓𝑎𝑝 mice was significantly lower than in the control group, but no significant difference was detected for vGluT1 expression. RNA-seq and qRT-PCR results showed that Mtnr1b knockout in astrocytes led to a decrease in the levels of gamma-aminobutyric acid sub-type A (GABAA) receptors and Kir2.2. Conclusions: The astrocyte-specific knockout in Mtnr1b cKO𝐺𝑓𝑎𝑝 mice results in anxiety-like behavior, which is caused by down-regulation of gamma-aminobutyric acid-ergic (GABAergic) synaptic function. |
| first_indexed | 2024-03-08T16:55:13Z |
| format | Article |
| id | doaj.art-b028b8f97a7a49c78e36ba1827dbaaa7 |
| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-03-08T16:55:13Z |
| publishDate | 2023-10-01 |
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| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-b028b8f97a7a49c78e36ba1827dbaaa72024-01-05T02:39:08ZengIMR PressJournal of Integrative Neuroscience0219-63522023-10-0122615410.31083/j.jin2206154S0219-6352(23)00635-6Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male MiceZijun Meng0Shipeng Guo1Xiangjun Dong2Qunxian Wang3Dongjie Hu4Xiaoqi Liu5Yanshuang Jiang6Liangye Ji7Jie Zhang8Weiyi Zhu9Weihui Zhou10Weihong Song11Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing, ChinaBackground: Astrocytes are essential for synaptic transmission, and their dysfunction can result in neuropsychiatric disorders such as anxiety and depression. Many studies have shown that global knockout of Melatonin receptor 2 (Mtnr1b) is associated with the development of various mental disorders. Aim: This study aimed to investigate the effects of astrocyte ablation of Mtnr1b on cognitive function and anxiety-like behavior in mice, as well as the potential biological mechanisms. Methods: A conditional Cre-loxP system allowing deletion of Mtnr1b from astrocytes was developed to investigate the specific role Mtnr1b. Control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were selected for cognitive function behavioral testing (Morris water maze test, novel object recognition test) and emotion-related behavioral testing (open field, elevated plus maze). After testing, brain tissue was collected and examined by immunofluorescence for the expression of neuronal nuclei (NeuN), glutamate decarboxylase 67 (GAD67), and vesicular glutamate transporter 1 (vGluT1). RNA-seq was performed on hippocampal tissue from control and Mtnr1b cKO𝐺𝑓𝑎𝑝 mice to identify differentially expressed genes. Additional confirmation of differential gene expression was performed using real-time quantitative polymerase chain reaction (qRT-PCR). Results: Mtnr1b cKO𝐺𝑓𝑎𝑝 mice were not significantly different from control mice in the Morris water maze and novel object recognition tests. Results from the open field and elevated plus maze tests showed that Mtnr1b cKO𝐺𝑓𝑎𝑝 mice exhibited significantly more anxiety-like behavior than did controls. Immunofluorescence revealed that the number of mature neurons did not differ significantly between Mtnr1b cKO𝐺𝑓𝑎𝑝 mice and controls. The expression of GAD67 in the hippocampal CA1 and CA3 areas of Mtnr1b cKO𝐺𝑓𝑎𝑝 mice was significantly lower than in the control group, but no significant difference was detected for vGluT1 expression. RNA-seq and qRT-PCR results showed that Mtnr1b knockout in astrocytes led to a decrease in the levels of gamma-aminobutyric acid sub-type A (GABAA) receptors and Kir2.2. Conclusions: The astrocyte-specific knockout in Mtnr1b cKO𝐺𝑓𝑎𝑝 mice results in anxiety-like behavior, which is caused by down-regulation of gamma-aminobutyric acid-ergic (GABAergic) synaptic function.https://www.imrpress.com/journal/JIN/22/6/10.31083/j.jin2206154astrocyteanxietygabamelatonin receptor 2 |
| spellingShingle | Zijun Meng Shipeng Guo Xiangjun Dong Qunxian Wang Dongjie Hu Xiaoqi Liu Yanshuang Jiang Liangye Ji Jie Zhang Weiyi Zhu Weihui Zhou Weihong Song Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice Journal of Integrative Neuroscience astrocyte anxiety gaba melatonin receptor 2 |
| title | Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice |
| title_full | Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice |
| title_fullStr | Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice |
| title_full_unstemmed | Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice |
| title_short | Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice |
| title_sort | astrocyte ablation of mtnr1b increases anxiety like behavior in adult male mice |
| topic | astrocyte anxiety gaba melatonin receptor 2 |
| url | https://www.imrpress.com/journal/JIN/22/6/10.31083/j.jin2206154 |
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