IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine
Abstract Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts rapid and sustained antidepressant actions. Preclinical studies demonstrated that the release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor in the medial prefrontal cortex (mPFC) is essential...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-05-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01943-9 |
| _version_ | 1811341320600420352 |
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| author | Satoshi Deyama Makoto Kondo Shoichi Shimada Katsuyuki Kaneda |
| author_facet | Satoshi Deyama Makoto Kondo Shoichi Shimada Katsuyuki Kaneda |
| author_sort | Satoshi Deyama |
| collection | DOAJ |
| description | Abstract Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts rapid and sustained antidepressant actions. Preclinical studies demonstrated that the release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor in the medial prefrontal cortex (mPFC) is essential for the antidepressant-like effects of ketamine. However, the role of other neurotrophic factors in the antidepressant-like effects of ketamine has not been fully investigated. Since the intra-mPFC infusion of insulin-like growth factor 1 (IGF-1) reportedly produced antidepressant-like effects, the present study examined the role of endogenous intra-mPFC IGF-1 signaling in the antidepressant-like actions of ketamine. In vivo microdialysis showed that ketamine (10 and 30 mg/kg) significantly increased extracellular IGF-1 levels in the mPFC of male C57BL/6J mice for at least 5 h. Infusion of an IGF-1 neutralizing antibody (nAb; 160 ng/side) into the mPFC 15 min before or 2 h after ketamine injection blocked the antidepressant-like effects of ketamine in three different behavioral paradigms (forced swim, female urine sniffing, and novelty-suppressed feeding tests were conducted 1, 3 and 4 days post-ketamine, respectively). The ketamine-like antidepressant-like actions of the intra-mPFC infusion of BDNF (100 ng/side) and IGF-1 (50 ng/side) respectively were not blocked by co-infused IGF-1 nAb and BDNF nAb (200 ng/side). Moreover, intra-mPFC infusion of IGF-1 nAb 2 h post-ketamine blocked the antidepressant-like effects of ketamine in a murine lipopolysaccharide (LPS)-induced depression model. Intra-mPFC IGF-1 infusion also produced antidepressant-like effects in the LPS-challenged mice via mechanistic target of rapamycin complex 1 activation. These results suggest that persistent release of IGF-1, independently of BDNF, in the mPFC is essential for the antidepressant-like actions of ketamine. |
| first_indexed | 2024-04-13T18:54:12Z |
| format | Article |
| id | doaj.art-0a03b7d4562f4e3589cf27f2360d4690 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-13T18:54:12Z |
| publishDate | 2022-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-0a03b7d4562f4e3589cf27f2360d46902022-12-22T02:34:18ZengNature Publishing GroupTranslational Psychiatry2158-31882022-05-0112111010.1038/s41398-022-01943-9IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamineSatoshi Deyama0Makoto Kondo1Shoichi Shimada2Katsuyuki Kaneda3Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityDepartment of Anatomy and Cell Biology, Graduate School of Medicine, Osaka City UniversityDepartment of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityAbstract Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts rapid and sustained antidepressant actions. Preclinical studies demonstrated that the release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor in the medial prefrontal cortex (mPFC) is essential for the antidepressant-like effects of ketamine. However, the role of other neurotrophic factors in the antidepressant-like effects of ketamine has not been fully investigated. Since the intra-mPFC infusion of insulin-like growth factor 1 (IGF-1) reportedly produced antidepressant-like effects, the present study examined the role of endogenous intra-mPFC IGF-1 signaling in the antidepressant-like actions of ketamine. In vivo microdialysis showed that ketamine (10 and 30 mg/kg) significantly increased extracellular IGF-1 levels in the mPFC of male C57BL/6J mice for at least 5 h. Infusion of an IGF-1 neutralizing antibody (nAb; 160 ng/side) into the mPFC 15 min before or 2 h after ketamine injection blocked the antidepressant-like effects of ketamine in three different behavioral paradigms (forced swim, female urine sniffing, and novelty-suppressed feeding tests were conducted 1, 3 and 4 days post-ketamine, respectively). The ketamine-like antidepressant-like actions of the intra-mPFC infusion of BDNF (100 ng/side) and IGF-1 (50 ng/side) respectively were not blocked by co-infused IGF-1 nAb and BDNF nAb (200 ng/side). Moreover, intra-mPFC infusion of IGF-1 nAb 2 h post-ketamine blocked the antidepressant-like effects of ketamine in a murine lipopolysaccharide (LPS)-induced depression model. Intra-mPFC IGF-1 infusion also produced antidepressant-like effects in the LPS-challenged mice via mechanistic target of rapamycin complex 1 activation. These results suggest that persistent release of IGF-1, independently of BDNF, in the mPFC is essential for the antidepressant-like actions of ketamine.https://doi.org/10.1038/s41398-022-01943-9 |
| spellingShingle | Satoshi Deyama Makoto Kondo Shoichi Shimada Katsuyuki Kaneda IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine Translational Psychiatry |
| title | IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine |
| title_full | IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine |
| title_fullStr | IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine |
| title_full_unstemmed | IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine |
| title_short | IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine |
| title_sort | igf 1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant like actions of ketamine |
| url | https://doi.org/10.1038/s41398-022-01943-9 |
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