Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

Abstract A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effec...

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Autores principales: Hanna Antila, Maria Ryazantseva, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Ipek Yalcin, Jesse Lindholm, Liisa Vesa, Vinicius Sato, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Plinio Casarotto, Leonard Khiroug, Sari Lauri, Tomi Taira, Eero Castrén, Tomi Rantamäki
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/9b0a9c01a2904ac9a4a5d9e945138f61
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spelling oai:doaj.org-article:9b0a9c01a2904ac9a4a5d9e945138f612021-12-02T16:08:01ZIsoflurane produces antidepressant effects and induces TrkB signaling in rodents10.1038/s41598-017-08166-92045-2322https://doaj.org/article/9b0a9c01a2904ac9a4a5d9e945138f612017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08166-9https://doaj.org/toc/2045-2322Abstract A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.Hanna AntilaMaria RyazantsevaDina PopovaPia SipiläRamon GuiradoSamuel KohtalaIpek YalcinJesse LindholmLiisa VesaVinicius SatoJoshua CordeiraHenri AutioMikhail KislinMaribel RiosSâmia JocaPlinio CasarottoLeonard KhirougSari LauriTomi TairaEero CastrénTomi RantamäkiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hanna Antila
Maria Ryazantseva
Dina Popova
Pia Sipilä
Ramon Guirado
Samuel Kohtala
Ipek Yalcin
Jesse Lindholm
Liisa Vesa
Vinicius Sato
Joshua Cordeira
Henri Autio
Mikhail Kislin
Maribel Rios
Sâmia Joca
Plinio Casarotto
Leonard Khiroug
Sari Lauri
Tomi Taira
Eero Castrén
Tomi Rantamäki
Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
description Abstract A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.
format article
author Hanna Antila
Maria Ryazantseva
Dina Popova
Pia Sipilä
Ramon Guirado
Samuel Kohtala
Ipek Yalcin
Jesse Lindholm
Liisa Vesa
Vinicius Sato
Joshua Cordeira
Henri Autio
Mikhail Kislin
Maribel Rios
Sâmia Joca
Plinio Casarotto
Leonard Khiroug
Sari Lauri
Tomi Taira
Eero Castrén
Tomi Rantamäki
author_facet Hanna Antila
Maria Ryazantseva
Dina Popova
Pia Sipilä
Ramon Guirado
Samuel Kohtala
Ipek Yalcin
Jesse Lindholm
Liisa Vesa
Vinicius Sato
Joshua Cordeira
Henri Autio
Mikhail Kislin
Maribel Rios
Sâmia Joca
Plinio Casarotto
Leonard Khiroug
Sari Lauri
Tomi Taira
Eero Castrén
Tomi Rantamäki
author_sort Hanna Antila
title Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
title_short Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
title_full Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
title_fullStr Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
title_full_unstemmed Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
title_sort isoflurane produces antidepressant effects and induces trkb signaling in rodents
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/9b0a9c01a2904ac9a4a5d9e945138f61
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