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Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system

Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine...

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Autores principales: Weckmann, Katja, Deery, Michael J., Howard, Julie A., Feret, Renata, Asara, John M., Dethloff, Frederik, Filiou, Michaela D., Iannace, Jamie, Labermaier, Christiana, Maccarrone, Giuseppina, Webhofer, Christian, Teplytska, Larysa, Lilley, Kathryn, Müller, Marianne B., Turck, Christoph W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694011/
https://www.ncbi.nlm.nih.gov/pubmed/29150633
http://dx.doi.org/10.1038/s41598-017-16183-x
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author Weckmann, Katja
Deery, Michael J.
Howard, Julie A.
Feret, Renata
Asara, John M.
Dethloff, Frederik
Filiou, Michaela D.
Iannace, Jamie
Labermaier, Christiana
Maccarrone, Giuseppina
Webhofer, Christian
Teplytska, Larysa
Lilley, Kathryn
Müller, Marianne B.
Turck, Christoph W.
author_facet Weckmann, Katja
Deery, Michael J.
Howard, Julie A.
Feret, Renata
Asara, John M.
Dethloff, Frederik
Filiou, Michaela D.
Iannace, Jamie
Labermaier, Christiana
Maccarrone, Giuseppina
Webhofer, Christian
Teplytska, Larysa
Lilley, Kathryn
Müller, Marianne B.
Turck, Christoph W.
author_sort Weckmann, Katja
collection PubMed
description Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures. Our data implicate mitochondrial energy metabolism and the antioxidant defense system as downstream effectors of the ketamine response. Specifically, ketamine tended to downregulate the adenosine triphosphate (ATP)/adenosine diphosphate (ADP) metabolite ratio which strongly correlated with forced swim test (FST) floating time. Furthermore, we found increased levels of enzymes that are part of the ‘oxidative phosphorylation’ (OXPHOS) pathway. Our study also suggests that ketamine causes less protein damage by rapidly decreasing reactive oxygen species (ROS) production and lend further support to the hypothesis that mitochondria have a critical role for mediating antidepressant action including the rapid ketamine response.
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spelling pubmed-56940112017-11-27 Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system Weckmann, Katja Deery, Michael J. Howard, Julie A. Feret, Renata Asara, John M. Dethloff, Frederik Filiou, Michaela D. Iannace, Jamie Labermaier, Christiana Maccarrone, Giuseppina Webhofer, Christian Teplytska, Larysa Lilley, Kathryn Müller, Marianne B. Turck, Christoph W. Sci Rep Article Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures. Our data implicate mitochondrial energy metabolism and the antioxidant defense system as downstream effectors of the ketamine response. Specifically, ketamine tended to downregulate the adenosine triphosphate (ATP)/adenosine diphosphate (ADP) metabolite ratio which strongly correlated with forced swim test (FST) floating time. Furthermore, we found increased levels of enzymes that are part of the ‘oxidative phosphorylation’ (OXPHOS) pathway. Our study also suggests that ketamine causes less protein damage by rapidly decreasing reactive oxygen species (ROS) production and lend further support to the hypothesis that mitochondria have a critical role for mediating antidepressant action including the rapid ketamine response. Nature Publishing Group UK 2017-11-17 /pmc/articles/PMC5694011/ /pubmed/29150633 http://dx.doi.org/10.1038/s41598-017-16183-x Text en © The Author(s) 2017 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/.
spellingShingle Article
Weckmann, Katja
Deery, Michael J.
Howard, Julie A.
Feret, Renata
Asara, John M.
Dethloff, Frederik
Filiou, Michaela D.
Iannace, Jamie
Labermaier, Christiana
Maccarrone, Giuseppina
Webhofer, Christian
Teplytska, Larysa
Lilley, Kathryn
Müller, Marianne B.
Turck, Christoph W.
Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
title Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
title_full Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
title_fullStr Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
title_full_unstemmed Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
title_short Ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
title_sort ketamine’s antidepressant effect is mediated by energy metabolism and antioxidant defense system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694011/
https://www.ncbi.nlm.nih.gov/pubmed/29150633
http://dx.doi.org/10.1038/s41598-017-16183-x
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