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A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling

Major depressive disorder (MDD) is a debilitating disease characterized by depressed mood, loss of interest or pleasure, suicidal ideation, and reduced motivation or hopelessness. Despite considerable research, mechanisms underlying MDD remain poorly understood, and current advances in treatment are...

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Autores principales: Kawatake-Kuno, Ayako, Murai, Toshiya, Uchida, Shusaku
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514675/
https://www.ncbi.nlm.nih.gov/pubmed/34658809
http://dx.doi.org/10.3389/fnbeh.2021.749180
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author Kawatake-Kuno, Ayako
Murai, Toshiya
Uchida, Shusaku
author_facet Kawatake-Kuno, Ayako
Murai, Toshiya
Uchida, Shusaku
author_sort Kawatake-Kuno, Ayako
collection PubMed
description Major depressive disorder (MDD) is a debilitating disease characterized by depressed mood, loss of interest or pleasure, suicidal ideation, and reduced motivation or hopelessness. Despite considerable research, mechanisms underlying MDD remain poorly understood, and current advances in treatment are far from satisfactory. The antidepressant effect of ketamine is among the most important discoveries in psychiatric research over the last half-century. Neurobiological insights into the ketamine’s effects have shed light on the mechanisms underlying antidepressant efficacy. However, mechanisms underlying the rapid and sustained antidepressant effects of ketamine remain controversial. Elucidating such mechanisms is key to identifying new therapeutic targets and developing therapeutic strategies. Accumulating evidence demonstrates the contribution of the glutamatergic pathway, the major excitatory neurotransmitter system in the central nervous system, in MDD pathophysiology and antidepressant effects. The hypothesis of a connection among the calcium signaling cascade stimulated by the glutamatergic system, neural plasticity, and epigenetic regulation of gene transcription is further supported by its associations with ketamine’s antidepressant effects. This review briefly summarizes the potential mechanisms of ketamine’s effects with a specific focus on glutamatergic signaling from a multiscale perspective, including behavioral, cellular, molecular, and epigenetic aspects, to provide a valuable overview of ketamine’s antidepressant effects.
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spelling pubmed-85146752021-10-15 A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling Kawatake-Kuno, Ayako Murai, Toshiya Uchida, Shusaku Front Behav Neurosci Neuroscience Major depressive disorder (MDD) is a debilitating disease characterized by depressed mood, loss of interest or pleasure, suicidal ideation, and reduced motivation or hopelessness. Despite considerable research, mechanisms underlying MDD remain poorly understood, and current advances in treatment are far from satisfactory. The antidepressant effect of ketamine is among the most important discoveries in psychiatric research over the last half-century. Neurobiological insights into the ketamine’s effects have shed light on the mechanisms underlying antidepressant efficacy. However, mechanisms underlying the rapid and sustained antidepressant effects of ketamine remain controversial. Elucidating such mechanisms is key to identifying new therapeutic targets and developing therapeutic strategies. Accumulating evidence demonstrates the contribution of the glutamatergic pathway, the major excitatory neurotransmitter system in the central nervous system, in MDD pathophysiology and antidepressant effects. The hypothesis of a connection among the calcium signaling cascade stimulated by the glutamatergic system, neural plasticity, and epigenetic regulation of gene transcription is further supported by its associations with ketamine’s antidepressant effects. This review briefly summarizes the potential mechanisms of ketamine’s effects with a specific focus on glutamatergic signaling from a multiscale perspective, including behavioral, cellular, molecular, and epigenetic aspects, to provide a valuable overview of ketamine’s antidepressant effects. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8514675/ /pubmed/34658809 http://dx.doi.org/10.3389/fnbeh.2021.749180 Text en Copyright © 2021 Kawatake-Kuno, Murai and Uchida. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Kawatake-Kuno, Ayako
Murai, Toshiya
Uchida, Shusaku
A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
title A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
title_full A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
title_fullStr A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
title_full_unstemmed A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
title_short A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
title_sort multiscale view of the mechanisms underlying ketamine’s antidepressant effects: an update on neuronal calcium signaling
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514675/
https://www.ncbi.nlm.nih.gov/pubmed/34658809
http://dx.doi.org/10.3389/fnbeh.2021.749180
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