Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway
Abstract To investigate the effects of ketamine on glucose uptake and glucose transporter (GLUT) expression in depressive-like mice. After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ket...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97758-7 |
| _version_ | 1818742683707899904 |
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| author | Xin Ouyang Zhengjia Wang Mei Luo Maozhou Wang Xing Liu Jiaxin Chen JianGuo Feng Jing Jia Xiaobin Wang |
| author_facet | Xin Ouyang Zhengjia Wang Mei Luo Maozhou Wang Xing Liu Jiaxin Chen JianGuo Feng Jing Jia Xiaobin Wang |
| author_sort | Xin Ouyang |
| collection | DOAJ |
| description | Abstract To investigate the effects of ketamine on glucose uptake and glucose transporter (GLUT) expression in depressive-like mice. After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ketamine on glucose uptake, production of lactate, and expression levels of GLUT, ERK1/2, AKT, and AMPK. Adult female C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS), 27 CUMS mice were randomly divided into the depression, ketamine (i.p.10 mg/kg), and FR180204 (ERK1/2 inhibitor, i.p.100 mg/kg) + ketamine group. Three mice randomly selected from each group were injected with 18F-FDG at 6 h after treatment. The brain tissue was collected at 6 h after treatment for p-ERK1/2 and GLUTs. Treatment with ketamine significantly increased glucose uptake, extracellular lactic-acid content, expression levels of GLUT3 and p-ERK in astrocytes and glucose uptake in the prefrontal cortex (P < 0.05), and the immobility time was significantly shortened in depressive-like mice (P < 0.01). An ERK1/2 inhibitor significantly inhibited ketamine-induced increases in the glucose uptake in depressive-like mice (P < 0.05), as well as prolonged the immobility time (P < 0.01). The expression levels of p-ERK1/2 and GLUT3 in depressive-like mice were significantly lower than those in normal control mice (P < 0.01). Ketamine treatment in depressive-like mice significantly increased the expression levels of p-ERK1/2 and GLUT3 in the prefrontal cortex (P < 0.01), whereas an ERK1/2 inhibitor significantly inhibited ketamine-induced increases (P < 0.01).Our present findings demonstrate that ketamine mitigated depressive-like behaviors in female mice by activating the ERK/GLUT3 signal pathway, which further increased glucose uptake in the prefrontal cortex. |
| first_indexed | 2024-12-18T02:16:25Z |
| format | Article |
| id | doaj.art-babd659a9127408cb059f0a78fc9170c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T02:16:25Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-babd659a9127408cb059f0a78fc9170c2022-12-21T21:24:22ZengNature PortfolioScientific Reports2045-23222021-09-0111111310.1038/s41598-021-97758-7Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathwayXin Ouyang0Zhengjia Wang1Mei Luo2Maozhou Wang3Xing Liu4Jiaxin Chen5JianGuo Feng6Jing Jia7Xiaobin Wang8Department of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityHeart Center, Beijing Anzhen Hospital, Captial Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Anesthesiology, The Affiliated Hospital of Southwest Medical UniversityAbstract To investigate the effects of ketamine on glucose uptake and glucose transporter (GLUT) expression in depressive-like mice. After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ketamine on glucose uptake, production of lactate, and expression levels of GLUT, ERK1/2, AKT, and AMPK. Adult female C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS), 27 CUMS mice were randomly divided into the depression, ketamine (i.p.10 mg/kg), and FR180204 (ERK1/2 inhibitor, i.p.100 mg/kg) + ketamine group. Three mice randomly selected from each group were injected with 18F-FDG at 6 h after treatment. The brain tissue was collected at 6 h after treatment for p-ERK1/2 and GLUTs. Treatment with ketamine significantly increased glucose uptake, extracellular lactic-acid content, expression levels of GLUT3 and p-ERK in astrocytes and glucose uptake in the prefrontal cortex (P < 0.05), and the immobility time was significantly shortened in depressive-like mice (P < 0.01). An ERK1/2 inhibitor significantly inhibited ketamine-induced increases in the glucose uptake in depressive-like mice (P < 0.05), as well as prolonged the immobility time (P < 0.01). The expression levels of p-ERK1/2 and GLUT3 in depressive-like mice were significantly lower than those in normal control mice (P < 0.01). Ketamine treatment in depressive-like mice significantly increased the expression levels of p-ERK1/2 and GLUT3 in the prefrontal cortex (P < 0.01), whereas an ERK1/2 inhibitor significantly inhibited ketamine-induced increases (P < 0.01).Our present findings demonstrate that ketamine mitigated depressive-like behaviors in female mice by activating the ERK/GLUT3 signal pathway, which further increased glucose uptake in the prefrontal cortex.https://doi.org/10.1038/s41598-021-97758-7 |
| spellingShingle | Xin Ouyang Zhengjia Wang Mei Luo Maozhou Wang Xing Liu Jiaxin Chen JianGuo Feng Jing Jia Xiaobin Wang Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway Scientific Reports |
| title | Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway |
| title_full | Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway |
| title_fullStr | Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway |
| title_full_unstemmed | Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway |
| title_short | Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway |
| title_sort | ketamine ameliorates depressive like behaviors in mice through increasing glucose uptake regulated by the erk glut3 signaling pathway |
| url | https://doi.org/10.1038/s41598-021-97758-7 |
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