Acute stress delays brain mitochondrial permeability transition pore opening

Authors

  • Cécile Batandier,

    Corresponding author
    1. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France
    2. U1055 – INSERM, Grenoble, France
    • Address correspondence and reprint requests to Cécile Batandier, Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, INSERM U1055, BP 53X, F-38041 Grenoble Cedex, France. E-mail: cecile.batandier@ujf-grenoble.fr

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  • Laurent Poulet,

    1. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France
    2. U1055 – INSERM, Grenoble, France
    3. Unité de Neurophysiologie du stress, Département Neurosciences et Contraintes Opérationnelles, Institut de Recherche Biomédicale des Armées, Paris, France
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  • Isabelle Hininger,

    1. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France
    2. U1055 – INSERM, Grenoble, France
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  • Karine Couturier,

    1. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France
    2. U1055 – INSERM, Grenoble, France
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  • Eric Fontaine,

    1. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France
    2. U1055 – INSERM, Grenoble, France
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  • Anne-Marie Roussel,

    1. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, Grenoble, France
    2. U1055 – INSERM, Grenoble, France
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  • Frédéric Canini

    1. Unité de Neurophysiologie du stress, Département Neurosciences et Contraintes Opérationnelles, Institut de Recherche Biomédicale des Armées, Paris, France
    2. Ecole du Val de Grâce, Paris, France
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  • In memoriam to Professor Xavier Leverve (1950–2010).

Abstract

Since emotional stress elicits brain activation, mitochondria should be a key component of stressed brain response. However, few studies have focused on mitochondria functioning in these conditions. In this work, we aimed to determine the effects of an acute restraint stress on rat brain mitochondrial functions, with a focus on permeability transition pore (PTP) functioning. Rats were divided into two groups, submitted or not to an acute 30-min restraint stress (Stress, S-group, vs. Control, C-group). Brain was removed immediately after stress. Mitochondrial respiration and enzymatic activities (complex I, complex II, hexokinase) were measured. Changes in PTP opening were assessed by the Ca2+ retention capacity. Cell signaling pathways relevant to the coupling between mitochondria and cell function (adenosine monophosphate-activated protein kinase, phosphatidylinositol 3-kinase, glycogen synthase kinase 3 beta, MAPK, and cGMP/NO) were measured. The effect of glucocorticoids was also assessed in vitro. Stress delayed (43%) the opening of PTP and resulted in a mild inhibition of complex I respiratory chain. This inhibition was associated with significant stress-induced changes in adenosine monophosphate-activated protein kinase signaling pathway without changes in brain cGMP level. In contrast, glucocorticoids did not modify PTP opening. These data suggest a rapid adaptive mechanism of brain mitochondria in stressed conditions, with a special focus on PTP regulation.

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In a rat model of acute restraint stress, we observed substantial changes in brain mitochondria functioning. Stress significantly (i) delays (43%) the opening of permeability transition pore (PTP) by the calcium (Ca2+), its main inductor and (ii) results in an inhibition of complex I in electron transport chain associated with change in AMPK signaling pathway. These data suggest an adaptive mechanism of brain mitochondria in stressed condition, with a special focus on PTP regulation.

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