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Bumetanide prevents brain trauma-induced depressive-like behavior

Goubert Emmanuelle, Altvater Marc, Rovira Marie-Noelle, Khalilov Ilgam, Mazzarino Morgane, Sebastiani Anne, Schaefer Michael, Rivera Claudio, View ORCID ProfilePellegrino Christophe
doi: https://doi.org/10.1101/443739
Goubert Emmanuelle
1INMED, Aix-Marseille Univ, INSERM, Marseille, France
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Altvater Marc
2Department of Anesthesiology and Research Center Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University Mainz
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Rovira Marie-Noelle
1INMED, Aix-Marseille Univ, INSERM, Marseille, France
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Khalilov Ilgam
1INMED, Aix-Marseille Univ, INSERM, Marseille, France
4Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia
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Mazzarino Morgane
1INMED, Aix-Marseille Univ, INSERM, Marseille, France
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Sebastiani Anne
2Department of Anesthesiology and Research Center Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University Mainz
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Schaefer Michael
2Department of Anesthesiology and Research Center Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University Mainz
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Rivera Claudio
1INMED, Aix-Marseille Univ, INSERM, Marseille, France
3Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland
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  • For correspondence: claudio.rivera@inserm.fr christophe.pellegrino@inserm.fr
Pellegrino Christophe
1INMED, Aix-Marseille Univ, INSERM, Marseille, France
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  • ORCID record for Pellegrino Christophe
  • For correspondence: claudio.rivera@inserm.fr christophe.pellegrino@inserm.fr
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Abstract

Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.

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Posted October 16, 2018.
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Bumetanide prevents brain trauma-induced depressive-like behavior
Goubert Emmanuelle, Altvater Marc, Rovira Marie-Noelle, Khalilov Ilgam, Mazzarino Morgane, Sebastiani Anne, Schaefer Michael, Rivera Claudio, Pellegrino Christophe
bioRxiv 443739; doi: https://doi.org/10.1101/443739
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Bumetanide prevents brain trauma-induced depressive-like behavior
Goubert Emmanuelle, Altvater Marc, Rovira Marie-Noelle, Khalilov Ilgam, Mazzarino Morgane, Sebastiani Anne, Schaefer Michael, Rivera Claudio, Pellegrino Christophe
bioRxiv 443739; doi: https://doi.org/10.1101/443739

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