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IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine

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 a...

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Autores principales: Deyama, Satoshi, Kondo, Makoto, Shimada, Shoichi, Kaneda, Katsuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110717/
https://www.ncbi.nlm.nih.gov/pubmed/35577782
http://dx.doi.org/10.1038/s41398-022-01943-9
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author Deyama, Satoshi
Kondo, Makoto
Shimada, Shoichi
Kaneda, Katsuyuki
author_facet Deyama, Satoshi
Kondo, Makoto
Shimada, Shoichi
Kaneda, Katsuyuki
author_sort Deyama, Satoshi
collection PubMed
description 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.
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spelling pubmed-91107172022-05-18 IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine Deyama, Satoshi Kondo, Makoto Shimada, Shoichi Kaneda, Katsuyuki Transl Psychiatry Article 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. Nature Publishing Group UK 2022-05-17 /pmc/articles/PMC9110717/ /pubmed/35577782 http://dx.doi.org/10.1038/s41398-022-01943-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Deyama, Satoshi
Kondo, Makoto
Shimada, Shoichi
Kaneda, Katsuyuki
IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110717/
https://www.ncbi.nlm.nih.gov/pubmed/35577782
http://dx.doi.org/10.1038/s41398-022-01943-9
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