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Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment

Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression. Despite a long history of clinical use, its mechanism of action remains poorly understood. Recently, a novel cellular mechanism of antidepressant action has been proposed: the phenotype of mature brain ne...

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Autores principales: Imoto, Yuki, Segi-Nishida, Eri, Suzuki, Hidenori, Kobayashi, Katsunori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335812/
https://www.ncbi.nlm.nih.gov/pubmed/28253930
http://dx.doi.org/10.1186/s13041-017-0288-9
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author Imoto, Yuki
Segi-Nishida, Eri
Suzuki, Hidenori
Kobayashi, Katsunori
author_facet Imoto, Yuki
Segi-Nishida, Eri
Suzuki, Hidenori
Kobayashi, Katsunori
author_sort Imoto, Yuki
collection PubMed
description Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression. Despite a long history of clinical use, its mechanism of action remains poorly understood. Recently, a novel cellular mechanism of antidepressant action has been proposed: the phenotype of mature brain neurons is transformed to immature-like one by antidepressant drug treatments. We show here that electroconvulsive stimulation (ECS), an animal model of ECT, causes profound changes in maturation-related phenotypes of neurons in the hippocampal dentate gyrus of adult mice. Single ECS immediately reduced expression of mature neuronal markers in almost entire population of dentate granule cells. After ECS treatments, granule cells showed some of physiological properties characteristic of immature granule cells such as higher somatic intrinsic excitability and smaller frequency facilitation at the detate-to-CA3 synapse. The rapid downregulation of maturation markers was suppressed by antagonizing glutamate NMDA receptors, but not by perturbing the serotonergic system. While single ECS caused short-lasting effects, repeated ECS induced stable changes in the maturation-related phenotypes lasting more than 2 weeks along with enhancement of synaptic excitation of granule cells. Augmentation of synaptic inhibition or blockade of NMDA receptors after repeated ECS facilitated regaining the initial mature phenotype, suggesting a role for endogenous neuronal excitation in maintaining the altered maturation-related phenotype probably via NMDA receptor activation. These results suggest that brief neuronal activation by ECS induces “dematuration” of the mature granule cells and that enhanced endogenous excitability is likely to support maintenance of such a demature state. The global increase in neuronal excitability accompanying this process may be relevant to the high efficacy of ECT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-017-0288-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-53358122017-03-07 Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment Imoto, Yuki Segi-Nishida, Eri Suzuki, Hidenori Kobayashi, Katsunori Mol Brain Research Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression. Despite a long history of clinical use, its mechanism of action remains poorly understood. Recently, a novel cellular mechanism of antidepressant action has been proposed: the phenotype of mature brain neurons is transformed to immature-like one by antidepressant drug treatments. We show here that electroconvulsive stimulation (ECS), an animal model of ECT, causes profound changes in maturation-related phenotypes of neurons in the hippocampal dentate gyrus of adult mice. Single ECS immediately reduced expression of mature neuronal markers in almost entire population of dentate granule cells. After ECS treatments, granule cells showed some of physiological properties characteristic of immature granule cells such as higher somatic intrinsic excitability and smaller frequency facilitation at the detate-to-CA3 synapse. The rapid downregulation of maturation markers was suppressed by antagonizing glutamate NMDA receptors, but not by perturbing the serotonergic system. While single ECS caused short-lasting effects, repeated ECS induced stable changes in the maturation-related phenotypes lasting more than 2 weeks along with enhancement of synaptic excitation of granule cells. Augmentation of synaptic inhibition or blockade of NMDA receptors after repeated ECS facilitated regaining the initial mature phenotype, suggesting a role for endogenous neuronal excitation in maintaining the altered maturation-related phenotype probably via NMDA receptor activation. These results suggest that brief neuronal activation by ECS induces “dematuration” of the mature granule cells and that enhanced endogenous excitability is likely to support maintenance of such a demature state. The global increase in neuronal excitability accompanying this process may be relevant to the high efficacy of ECT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-017-0288-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-02 /pmc/articles/PMC5335812/ /pubmed/28253930 http://dx.doi.org/10.1186/s13041-017-0288-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Imoto, Yuki
Segi-Nishida, Eri
Suzuki, Hidenori
Kobayashi, Katsunori
Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
title Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
title_full Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
title_fullStr Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
title_full_unstemmed Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
title_short Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
title_sort rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335812/
https://www.ncbi.nlm.nih.gov/pubmed/28253930
http://dx.doi.org/10.1186/s13041-017-0288-9
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