Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action

Summary: Ketamine is a noncompetitive glutamatergic N-methyl-d-aspartate receptor (NMDAR) antagonist that exerts rapid antidepressant effects. Preclinical studies identify eukaryotic elongation factor 2 kinase (eEF2K) signaling as essential for the rapid antidepressant action of ketamine. Here, we c...

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Autores principales:	Kanzo Suzuki, Ji-Woon Kim, Elena Nosyreva, Ege T. Kavalali, Lisa M. Monteggia
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	eEF2K RARα synaptic scaling rapid antidepressant action Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6dd69221221e448c8ccdfbb132cd2ff5
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spelling	oai:doaj.org-article:6dd69221221e448c8ccdfbb132cd2ff52021-11-04T04:29:08ZConvergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action2211-124710.1016/j.celrep.2021.109918https://doaj.org/article/6dd69221221e448c8ccdfbb132cd2ff52021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013917https://doaj.org/toc/2211-1247Summary: Ketamine is a noncompetitive glutamatergic N-methyl-d-aspartate receptor (NMDAR) antagonist that exerts rapid antidepressant effects. Preclinical studies identify eukaryotic elongation factor 2 kinase (eEF2K) signaling as essential for the rapid antidepressant action of ketamine. Here, we combine genetic, electrophysiological, and pharmacological strategies to investigate the role of eEF2K in synaptic function and find that acute, but not chronic, inhibition of eEF2K activity induces rapid synaptic scaling in the hippocampus. Retinoic acid (RA) signaling also elicits a similar form of rapid synaptic scaling in the hippocampus, which we observe is independent of eEF2K functioni. The RA signaling pathway is not required for ketamine-mediated antidepressant action; however, direct activation of the retinoic acid receptor α (RARα) evokes rapid antidepressant action resembling ketamine. Our findings show that ketamine and RARα activation independently elicit a similar form of multiplicative synaptic scaling that is causal for rapid antidepressant action.Kanzo SuzukiJi-Woon KimElena NosyrevaEge T. KavalaliLisa M. MonteggiaElsevierarticleeEF2KRARαsynaptic scalingrapid antidepressant actionBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109918- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	eEF2K RARα synaptic scaling rapid antidepressant action Biology (General) QH301-705.5
spellingShingle	eEF2K RARα synaptic scaling rapid antidepressant action Biology (General) QH301-705.5 Kanzo Suzuki Ji-Woon Kim Elena Nosyreva Ege T. Kavalali Lisa M. Monteggia Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
description	Summary: Ketamine is a noncompetitive glutamatergic N-methyl-d-aspartate receptor (NMDAR) antagonist that exerts rapid antidepressant effects. Preclinical studies identify eukaryotic elongation factor 2 kinase (eEF2K) signaling as essential for the rapid antidepressant action of ketamine. Here, we combine genetic, electrophysiological, and pharmacological strategies to investigate the role of eEF2K in synaptic function and find that acute, but not chronic, inhibition of eEF2K activity induces rapid synaptic scaling in the hippocampus. Retinoic acid (RA) signaling also elicits a similar form of rapid synaptic scaling in the hippocampus, which we observe is independent of eEF2K functioni. The RA signaling pathway is not required for ketamine-mediated antidepressant action; however, direct activation of the retinoic acid receptor α (RARα) evokes rapid antidepressant action resembling ketamine. Our findings show that ketamine and RARα activation independently elicit a similar form of multiplicative synaptic scaling that is causal for rapid antidepressant action.
format	article
author	Kanzo Suzuki Ji-Woon Kim Elena Nosyreva Ege T. Kavalali Lisa M. Monteggia
author_facet	Kanzo Suzuki Ji-Woon Kim Elena Nosyreva Ege T. Kavalali Lisa M. Monteggia
author_sort	Kanzo Suzuki
title	Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
title_short	Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
title_full	Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
title_fullStr	Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
title_full_unstemmed	Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
title_sort	convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6dd69221221e448c8ccdfbb132cd2ff5
work_keys_str_mv	AT kanzosuzuki convergenceofdistinctsignalingpathwaysonsynapticscalingtotriggerrapidantidepressantaction AT jiwoonkim convergenceofdistinctsignalingpathwaysonsynapticscalingtotriggerrapidantidepressantaction AT elenanosyreva convergenceofdistinctsignalingpathwaysonsynapticscalingtotriggerrapidantidepressantaction AT egetkavalali convergenceofdistinctsignalingpathwaysonsynapticscalingtotriggerrapidantidepressantaction AT lisammonteggia convergenceofdistinctsignalingpathwaysonsynapticscalingtotriggerrapidantidepressantaction
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Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action

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