New Results
TrkB signaling underlies the rapid antidepressant effects of isoflurane
Hanna Antila, Plinio Casarotto, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Maria Ryazantseva, Liisa Vesa, Jesse Lindholm, Ipek Yalcin, Vinicius Sato, Helka Gööse, Sarah Lemprièref, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Leonard Khiroug, Sari Lauri, Markku Varjosalo, Seth G.N. Grant, Tomi Taira, Eero Castrén, Tomi Rantamäki
doi: https://doi.org/10.1101/084525
Hanna Antila
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Plinio Casarotto
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Dina Popova
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Pia Sipilä
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Ramon Guirado
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Samuel Kohtala
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
bDivision of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Maria Ryazantseva
bDivision of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Liisa Vesa
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Jesse Lindholm
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
bDivision of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Ipek Yalcin
cInstitut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, FR-67084 Strasbourg Cedex, France.
Vinicius Sato
dSchool of Pharmaceutical Sciences of Ribeirão Preto 14040-903, Brazil.
Helka Gööse
eInstitute of Biotechnology, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Sarah Lemprièref
fUniversity of Edinburgh, Edinburgh, UK
Joshua Cordeira
gTufts University, Boston, MA, USA.
Henri Autio
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Mikhail Kislin
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Maribel Rios
gTufts University, Boston, MA, USA.
Sâmia Joca
dSchool of Pharmaceutical Sciences of Ribeirão Preto 14040-903, Brazil.
Leonard Khiroug
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Sari Lauri
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
bDivision of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Markku Varjosalo
eInstitute of Biotechnology, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Seth G.N. Grant
fUniversity of Edinburgh, Edinburgh, UK
Tomi Taira
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
hDepartment of Veterinary Biosciences, Faculty of Veterinary Medicine P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Eero Castrén
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
Tomi Rantamäki
aNeuroscience Center, P.O. Box 56, FI-00014 University of Helsinki, Helsinki, Finland.
bDivision of Physiology and Neuroscience, Department of Biosciences, Faculty of Biological and Environmental Sciences, P.O. Box 66, FI-00014 University of Helsinki, Helsinki, Finland.
Abstract
Neuronal plasticity induced by signaling through BDNF receptor TrkB has been implicated in the actions of antidepressants, including the rapid-acting antidepressant ketamine. We show that isoflurane induced transphosphorylation of TrkB by Src family kinases, stimulates the mTor signaling pathway and promotes neuronal plasticity and antidepressant-like behavior in rodents. Our findings provide a neurobiological basis for the clinically observed antidepressant effects of isoflurane and encourage its further evaluation as a rapid-acting antidepressant treatment devoid of the psychotomimetic side effects of ketamine.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted November 02, 2016.
TrkB signaling underlies the rapid antidepressant effects of isoflurane
Hanna Antila, Plinio Casarotto, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Maria Ryazantseva, Liisa Vesa, Jesse Lindholm, Ipek Yalcin, Vinicius Sato, Helka Gööse, Sarah Lemprièref, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Leonard Khiroug, Sari Lauri, Markku Varjosalo, Seth G.N. Grant, Tomi Taira, Eero Castrén, Tomi Rantamäki
bioRxiv 084525; doi: https://doi.org/10.1101/084525
TrkB signaling underlies the rapid antidepressant effects of isoflurane
Hanna Antila, Plinio Casarotto, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Maria Ryazantseva, Liisa Vesa, Jesse Lindholm, Ipek Yalcin, Vinicius Sato, Helka Gööse, Sarah Lemprièref, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Leonard Khiroug, Sari Lauri, Markku Varjosalo, Seth G.N. Grant, Tomi Taira, Eero Castrén, Tomi Rantamäki
bioRxiv 084525; doi: https://doi.org/10.1101/084525
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