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14 results on '"Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France"'

1. Comparing meditative scuba diving versus multisport activities to improve post-traumatic stress disorder symptoms: a pilot, randomized controlled clinical trial

Author

Lionel Gibert, Mathieu Coulange, Jean-Charles Reynier, Frédéric Le Quiniat, Aymeric Molle, Frédéric Bénéton, Vincent Meurice, Jean Arthur Micoulaud, Marion Trousselard, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Hôpital Paul Brousse, Université Paris-Saclay, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France (IRBA), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], and CHU de Bordeaux Pellegrin [Bordeaux]

Subjects
Adult, Male, Diving, scuba diving, PTSD, Pilot Projects, Proof of Concept Study, Stress Disorders, Post-Traumatic, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SCCO.PSYC]Cognitive science/Psychology, Humans, Female, terrorist attack, Mindfulness, Veterans
Abstract

International audience; Background Post-Traumatic Stress Disorder (PTSD) is a chronic and disabling disease that currently has no fully effective therapeutic solution. Complementary approaches, such as relaxation, sport, or meditation, could be therapeutic aids for symptom reduction. Scuba diving combines sport and mindfulness training and has been found to have a positive effect on chronic stress and PTSD. Objectives The first objective of this pilot study is to compare the effectiveness of diving associated with mindfulness exercises (the Bathysmed (R) protocol) with multisport activity in reducing PTSD symptoms. The secondary objective is to compare the impact of the Bathysmed (R) protocol on mindfulness functioning in the two groups of subjects suffering from PTSD. Method This proof-of-concept took the form of a controlled randomized clinical trial. The primary endpoint was the severity of PTSD symptoms, measured by the PCL-5 (PTSD Check List) scale. Half of the group were exposed to the Bathysmed (R) protocol (the experimental condition), and the other half to a non-specific multisport program. Results Bathysmed (R) protocol improved PCL-5 scores more than the multisport program but the result was not significant. The protocol was significantly better than the multisport activity in reducing intrusion symptoms of PTSD after one month. Globally, trait mindfulness scores improved up to one month after the course, but the result was not significant. Three months after the course, there was no difference between the two groups with regard to PCL-5 and Freiburg Mindfulness Inventory scores.. Conclusion Our study demonstrates the value of the Bathysmed (R) protocol even though it suffers from a lack of power and could only obtain partial but encouraging results. Mindfulness must be practiced over the long term to achieve stable benefits. This probably explains why no differences persisted three months after the course. Further work is needed to confirm the initial results obtained with this pilot study.

Published
2022

2. Treatment of allergic rhinitis during and outside the pollen season using mobile technology. a MASK study

Author

Sietze Reitsma, Josep M. Antó, Dermot Ryan, C. Stellato, W. Czarlewski, S. Shamai, G. De Vries, Elísio Costa, E. Melen, Esben Eller, Tari Haahtela, Carsten Bindslev-Jensen, Dana Wallace, Ricardo Pio Monti, P. V. Tomazic, A. Yorgancioglu, Oliver Pfaar, Michel Thibaudon, B. Samolinski, Asiyah Sheikh, Daniel Laune, J. C. Ivancevich, M. Morais-Almeida, Niels H. Chavannes, Ralph Mösges, Lorenzo Cecchi, Susan Waserman, Regina Roller-Wirnsberger, V. Cardona, Piotr Kuna, P. Devillier, M. van Eerd, Mikhail Sofiev, Rute Almeida, I. Kull, Isabelle Bosse, J Mullol, A Valero, Ioana Agache, João Fonseca, Violeta Kvedariene, J. F. Fontaine, A. Bedbrook, Sylvie Arnavielhe, Fotis Psarros, Jean Bousquet, Peter Schmid-Grendelmeier, A. A. Cruz, Ludger Klimek, Ruta Dubakiene, Nhân Pham-Thi, Judith Garcia-Aymerich, Benoit Pugin, G. De Feo, Thomas B. Casale, Ruth Murray, Nikolaos G. Papadopoulos, Annabelle Bédard, I. J. Ansotegui, Claus Bachert, Magnus Wickman, Michael Makris, J. Correia da Sousa, Emmanuel P. Prokopakis, Ana Todo-Bom, Enrica Menditto, Xavier Basagaña, W. J. Fokkens, Peter Hellings, Gabrielle L. Onorato, Sinthia Bosnic-Anticevich, D. Larenas-Linnemann, François Spertini, A. Valiulis, R. Emuzyte, M. T. Ventura, Sanna Toppila-Salmi, I. Annesi-Maesano, Maddalena Illario, Erkka Valovirta, Bedard, A., Basagana, X., Anto, J. M., Garcia-Aymerich, J., Devillier, P., Arnavielhe, S., Bedbrook, A., Onorato, G. L., Czarlewski, W., Murray, R., Almeida, R., Fonseca, J. A., Correia da Sousa, J., Costa, E., Morais-Almeida, M., Todo-Bom, A., Cecchi, L., De Feo, G., Illario, M., Menditto, E., Monti, R., Stellato, C., Ventura, M. T., Annesi-Maesano, I., Bosse, I., Fontaine, J. F., Pham-Thi, N., Thibaudon, M., Schmid-Grendelmeier, P., Spertini, F., Chavannes, N. H., Fokkens, W. J., Reitsma, S., Dubakiene, R., Emuzyte, R., Kvedariene, V., Valiulis, A., Kuna, P., Samolinski, B., Klimek, L., Mosges, R., Pfaar, O., Shamai, S., Roller-Wirnsberger, R. E., Tomazic, P. V., Ryan, D., Sheikh, A., Haahtela, T., Toppila-Salmi, S., Valovirta, E., Cardona, V., Mullol, J., Valero, A., Makris, M., Papadopoulos, N. G., Prokopakis, E. P., Psarros, F., Bachert, C., Hellings, P. W., Pugin, B., Bindslev-Jensen, C., Eller, E., Kull, I., Melen, E., Wickman, M., De Vries, G., van Eerd, M., Agache, I., Ansotegui, I. J., Bosnic-Anticevich, S., Cruz, A. A., Casale, T., Ivancevich, J. C., Larenas-Linnemann, D. E., Sofiev, M., Wallace, D., Waserman, S., Yorgancioglu, A., Laune, D., Bousquet, J., Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), KYomed INNOV [Montpellier], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Centre de Soins d'enseignement et de recherche dentaires [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Allergist [La Rochelle], Allergist [Reims], Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France (IRBA), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Réseau National de Surveillance Aérobiologique (RNSA), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Allergy, IMPACT, Respiratory Medicine and Allergy, Review, Allergic rhinitis, 0302 clinical medicine, Anti-histamines, Corticosteroids, ICT, MASK, Mobile health, Treatment, Allergic symptoms, Medicine and Health Sciences, Immunology and Allergy, Medicine, Corticosteroid, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Lungmedicin och allergi, 0303 health sciences, Anti-histamine, IMPAIRMENT, 3. Good health, Life Sciences & Biomedicine, medicine.drug, Pulmonary and Respiratory Medicine, Immunology, AZELASTINE/FLUTICASONE, Mometasone furoate, PERSON-CENTERED CARE, Fluticasone propionate, 03 medical and health sciences, INTERMITTENT, Allergic rhiniti, 030304 developmental biology, Asthma, Science & Technology, Pollen season, business.industry, GUIDANCE, AIR-POLLUTION, medicine.disease, SEVERITY, 030228 respiratory system, ASTHMA, Observational study, business, Demography
Abstract

Background The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods The Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. Conclusions This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

Published
2020

3. Gait initiation and embedded sensors: assessment of the risk of falling at home in elderly

Author

Coudrat, Laure, Bascou, Joseph, Kop, Jean-Luc, Jacob, Christel, Rivasseau-Jonveaux, Thérèse, Trousselard, Marion, Dinet, Jérôme, Laboratoire lorrain de psychologie et neurosciences de la dynamique des comportements (2LPN), Université de Lorraine (UL), Institution Nationale des Invalides - Centre d’Etudes et de Recherche sur l’Appareillage des Handicapés (INI/CERAH), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, and Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress

Subjects
[SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020

4. Social context increases ultrasonic vocalizations during restraint in adult mice

Author

Sylvie Granon, E. Lefebvre, Frédéric Chauveau, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France (IRBA), and Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress

Subjects
Male, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Emotions, Experimental and Cognitive Psychology, Audiology, Restraint, Social Environment, Social interaction, Arousal, 03 medical and health sciences, Call rate, Mice, 0302 clinical medicine, medicine, Animals, Ultrasonics, Social isolation, Free moving, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Social communication, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Ultrasonic vocalization, Social environment, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Social relation, Social Isolation, medicine.symptom, Vocalization, Animal, Psychology, 030217 neurology & neurosurgery, Social motivation
Abstract

International audience; Adult mice emit many ultrasonic vocalizations (USVs) during social interaction tasks, but only a few studies have yet reported USVs in stressed adult mice. Our aim was to study which experimental conditions favor USV emission during behaviors associated with different emotional states. As USVs likely mediate social communication, we hypothesized that temporary social isolation followed by exposure to a novel social congener would promote USV emission. USVs were recorded in three different behavioral paradigms: restraint, free moving in a new environment, and during a social interaction task. We compared USV emission, with or without the presence of a social congener, in animals socially isolated during different periods (0, 6 or 21 days). Social isolation decreased the number of USVs during free moving, whereas it increased during restraint. During the social interaction task, animals produced high-frequency USVs (median: 72.6 kHz, 25-75% range: 67.6-78.2 kHz), especially when the social partner was active and social motivation was high. During restraint, presence of a social congener increased the call rate of low-frequency USVs (median: 52.4 kHz, 25-75% range: 44.8-56.5 kHz). USV frequency followed two unimodal distributions that distinguished low-frequency USVs (≤ 60 kHz) mainly emitted during free-moving (90.9% of total USVs) and restraint (93.1%) conditions, from high-frequency USVs (> 60 kHz) mainly emitted during the social interaction task (85.1% of total USVs). The present study confirms that USV call rate and frequency depend on behavioral states, and provides evidence that the presence of a congener promotes ultrasonic vocalizations in restrained adult mice.

Published
2020

5. Trends in severe opioid-related poisonings and fatalities reported to the Paris poison control center – a 10-year retrospective observational study

Author

Marc Deveaux, Jérôme Langrand, Dominique Vodovar, Weniko Caré, Jean-Claude Alvarez, Frédéric Dorandeu, Bruno Mégarbane, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, École du Val de Grâce (EVDG), Institut National de la Santé et de la Recherche Médicale, Inserm: UMR-1107, and The authors would like to acknowledge Prof. Nicolas Authier from the Department of medical pharmacology, French Monitoring Center of analgesic drugs (OFMA), INSERM UMR-1107, Clermont-Ferrand University Hospital, Clermont-Ferrand, France, for providing us with useful bibliographical information.

Subjects
Adult, Male, medicine.medical_specialty, Paris, Poison Control Centers, Time Factors, Adolescent, Narcotic Antagonists, [SDV]Life Sciences [q-bio], Propoxyphene, Poison control, 030226 pharmacology & pharmacy, Drug Prescriptions, fentanyl, 03 medical and health sciences, Young Adult, 0302 clinical medicine, fatality, Naloxone, Cause of Death, medicine, Humans, Pharmacology (medical), Retrospective Studies, Pharmacology, naloxone, business.industry, Opioid overdose, Middle Aged, medicine.disease, Opioid-Related Disorders, Poison control center, 3. Good health, Analgesics, Opioid, poisoning, Suicide, Opioid, Emergency medicine, opioid, Female, epidemiology, Tramadol, business, 030217 neurology & neurosurgery, medicine.drug, Methadone
Abstract

International audience; France is experiencing an increase in the number of opioid prescriptions and related fatalities. We carried out a retrospective observational study using data from the Paris PCC over a 10-year period. The main objective was to obtain an epidemiological description of the severe reported cases. The secondary objectives were to assess the evolution of the number of these cases and their severity defined by the use of fentanyl and its derivatives, the use of the opioid-poisoning treatment naloxone, and the number of fatalities. During 2008–2017, 268 511 cases were recorded, including 1 122 cases of opioid-related poisoning that required medical management. These poisonings involved tramadol (43%), codeine (25%), dextropropoxyphene (13%), and morphine (8%); most resulted from self-exposure (60%). During the 10-year study period, 130 opioid-related fatalities were recorded in the Paris area, mainly resulting from suicides (39%) in men and were attributed to morphine (27%), tramadol (24%), and methadone (21%). We did not identify an increase in the number of severe opioid-related poisonings or fatalities or in the use of fentanyl or its derivatives. Conversely, we observed an increase in the use of naloxone, suggesting an increase in the severity of opioid poisonings. Our findings show that, until 2017, the opioid overdose epidemiology in the Paris area is different to that in the USA. The systematic analysis of data from the PCCs could be a good tool for health monitoring. To assess trends in France, a national study over a longer period would also be useful.

Published
2020

6. Suicide among physicians and health-care workers: A systematic review and meta-analysis

Author

Bruno Pereira, Marion Trousselard, Frédéric Dutheil, Valentin Navel, François-Xavier Lesage, Claire Aubert, Julien S. Baker, Farès Moustafa, Martial Mermillod, Michaël Dambrun, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service Santé Travail Environnement [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, WittyFit, Australian Catholic University (ACU), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Pôle Urgences [CHU Clermont-Ferrand], Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Centre for Health and Exercise Science Research, Department of Sport, Physical Education and Health, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France (IRBA), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université de Montpellier (UM)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université Montpellier 1 (UM1), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Ophtalmologie [CHU Clermont-Ferrand], Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université de Montpellier (UM)

Subjects
Medical Doctors, Health Care Providers, Declaration, Nurses, Poison control, [SHS.PSY]Humanities and Social Sciences/Psychology, Cochrane Library, Suicide prevention, Occupational safety and health, Database and Informatics Methods, Mathematical and Statistical Techniques, 0302 clinical medicine, Risk Factors, Health care, Medicine and Health Sciences, Medical Personnel, 030212 general & internal medicine, Database Searching, 050207 economics, Suicidal ideation, Multidisciplinary, 050208 finance, High prevalence, Statistics, 05 social sciences, Metaanalysis, 16. Peace & justice, Checklist, 3. Good health, Suicide, Professions, Meta-analysis, Physical Sciences, Medicine, medicine.symptom, Research Article, medicine.medical_specialty, Health Personnel, Science, Research and Analysis Methods, 03 medical and health sciences, General Practitioners, Physicians, Mental Health and Psychiatry, 0502 economics and business, medicine, Humans, Statistical Methods, Surgeons, Suicide attempt, business.industry, Health Care, Family medicine, People and Places, Population Groupings, business, Mathematics, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: Medical-related professions are at high suicide risk. However, data are contradictory and comparisons were not made between gender, occupation and specialties, epochs of times. Methods: To conduct a systematic review and meta-analysis on suicide risk among health-care workers, were searched in PubMed, Cochrane Library, Science Direct and Embase databases without language restriction on April 2019. We stratified results by gender, countries, time, and specialties. Estimates were pooled using random-effect meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Information on suicides, suicidal attempts, and suicidal ideation, and related-characteristics were retrieved from national or local specific registers or case records. In addition, suicide attempts and suicidal ideation were also retrieved from questionnaires (paper or internet). Findings: The overall SMR for suicide in physicians was 1.44 (95CI 1.16, 1.72) with an important heterogeneity (I2=93.9%, p

Published
2019

7. Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses

Author

Djoher Nora Abrous, Beatriz Rodriguez-Grande, Aleksandra Ichkova, Jérôme Badaut, Andre Obenaus, Marie-Line Fournier, Justine Aussudre, Jeong Bin Lee, Elizabeth Haddad, Michael Ogier, Muriel Koehl, Tifenn Clément, Frédéric Canini, Plasma Science and Application Laboratory (PSAL), University of Texas at Dallas [Richardson] (UT Dallas), Neuroinflammation: imagerie et thérapie de la sclérose en plaques, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Traumatic brain injury, Biology, neuroinflammation, histology, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Head Injuries, Closed, Glial Fibrillary Acidic Protein, medicine, Animals, Gliosis, Prefrontal cortex, Brain Concussion, Neuroinflammation, Glial fibrillary acidic protein, Dentate gyrus, traumatic brain injury, Brain, Nestin, medicine.disease, Magnetic Resonance Imaging, Astrogliosis, 030104 developmental biology, medicine.anatomical_structure, Neurology, Astrocytes, Brain Injuries, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery, Astrocyte, MRI
Abstract

International audience; Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long-term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post-mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following brain injury, potentially leading to significant brain dysfunction. However, such alterations have never been investigated in the context of juvenile mTBI (jmTBI). A closed-head injury model was used to study jmTBI on postnatal-day 17 mice. Astrogliosis was evaluated using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days postinjury (dpi). In vivo T2-weighted-imaging (T2WI) and diffusion tensor imaging (DTI) were performed at 7 and 30 dpi to examine tissue level structural alterations. Increased GFAP-labeling was observed up to 30 dpi in the ipsilateral SSC, the initial site of the impact. However, vimentin and nestin expression was not perturbed by jmTBI. The morphology of GFAP positive cells was significantly altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with magnetic resonance imaging changes. T2WI and DTI values were significantly altered at 30 dpi within these brain regions most prominently in regions distant from the impact site. Our data show that jmTBI triggers changes in astrocytic phenotype with a distinct spatiotemporal pattern. We speculate that the presence and time course of astrogliosis may contribute to pathophysiological processes and long-term structural alterations following jmTBI.

Published
2019

8. Behavioral and Noradrenergic Sensitizations in Vulnerable Traumatized Rats Suggest Common Bases with Substance Use Disorders

Author

Fréderic Chauveau, Pascale Gisquet-Verrier, Jean-Pol Tassin, Claire Le Dorze, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France (IRBA), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Institut des Neurosciences de Paris-Saclay (Neuro-PSI), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, Microdialysis, Substance-Related Disorders, media_common.quotation_subject, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Infralimbic cortex, Neuroscience (miscellaneous), Motor Activity, Prefrontal cortex, Rats, Sprague-Dawley, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Norepinephrine, 0302 clinical medicine, Internal medicine, medicine, Limbic System, Animals, Amphetamine, Sensitization, media_common, Post-traumatic stress disorder (PTSD), Behavior, Animal, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Addiction, Dopaminergic, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, Rats, Single prolonged stress (SPS), Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Neurology, business, 030217 neurology & neurosurgery, medicine.drug, Monoaminergic uncoupling
Abstract

International audience; The aim of the present study was to strengthen our hypothesis of a common physiological basis for post-traumatic stress disorder (PTSD) and substance use disorders. This paper investigates the possibility that rats exposed to a PTSD model exhibit noradrenergic and behavioral sensitization, as observed following repeated drugs of abuse injections. First, rats received a single prolonged stress (SPS), combining three consecutive stressors. They were then tested, 2 weeks after the trauma for PTSD-like symptoms to discriminate between vulnerable and resilient rats. When microdialysis was performed in the prelimbic cortex (Experiment 1), larger increases of noradrenaline (NA) release in response to amphetamine were observed in vulnerable rats when compared to control and resilient animals. Experiment 2 showed that trauma-vulnerable rats exhibited increases in locomotor activity relative to controls, in response to an exposure to trauma-associated cues. These data demonstrate that a single trauma exposure induces in vulnerable animals both, a noradrenergic sensitization evidenced within the prelimbic cortex and behavioral sensitization obtained after a physiologic activation of the noradrenergic system. However, Experiment 3 showed that when NA system was activated by amphetamine (1 mg/kg), a decrease in behavioral sensitization was obtained in vulnerable rats. We proposed that this decreased locomotor activity results from an additional stress-induced increased reactivity of mesocortical dopaminergic neurons, known to counteract the consequences of cortical noradrenergic release in rats. These results support our hypothesis that noradrenergic sensitization represents a common physiological basis, involved both in PTSD and drug addiction and suggest new common therapeutic approaches for these pathologies.

Published
2018

9. Acute stress delays brain mitochondrial permeability transition pore opening

Author

Isabelle Hininger, Eric Fontaine, Laurent Poulet, Cécile Batandier, Frédéric Canini, Karine Couturier, Anne-Marie Roussel, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, and ANR-07-PNRA-0003,CERVIRMIT,Cerveau, résistance à l'insuline et mitochondrie :Rôle neuroprotecteur des polyphénols de la cannelle dans un modèle animal de syndrome métabolique(2007)

Subjects
Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Respiratory chain, Mitochondrion, Mitochondrial Membrane Transport Proteins, Biochemistry, Permeability, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Oxygen Consumption, Internal medicine, medicine, Animals, Rats, Wistar, Protein kinase A, Cyclic GMP, Glucocorticoids, GSK3B, ComputingMilieux_MISCELLANEOUS, Hexokinase, Mitochondrial Permeability Transition Pore, Chemistry, Brain, Adenosine, Rats, Cell biology, Endocrinology, Mitochondrial permeability transition pore, Calcium, Signal transduction, Stress, Psychological, Signal Transduction, medicine.drug
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 Ca(2+) 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. 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 (Ca(2+) ), 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.

Published
2014

10. Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity

Author

Frédéric Canini, Marion Trousselard, Julien Thomasson, Frédéric Chauveau, Betty Poly-Thomasson, Sylvie Granon, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Institut des Neurosciences Paris-Saclay (NeuroPSI), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Time Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Microdialysis, Infralimbic cortex, Short-term memory, Hippocampus, Prefrontal Cortex, Proto-Oncogene Proteins c-fyn, Amygdala, 03 medical and health sciences, Mice, 0302 clinical medicine, Neuropeptide S, medicine, Animals, Pharmacology (medical), Prefrontal cortex, Maze Learning, Biological Psychiatry, Sleep restriction, Pharmacology, Analysis of Variance, Memory Disorders, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Neuropeptides, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Mice, Inbred C57BL, Psychiatry and Mental health, 030104 developmental biology, medicine.anatomical_structure, Memory, Short-Term, Neurology, Short term memory, Sleep Deprivation, Neurology (clinical), Psychology, Neuroscience, 030217 neurology & neurosurgery, Basolateral amygdala
Abstract

International audience; Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour.

Published
2016

11. Molecular gene expression following blunt and rotational models of traumatic brain injury parallel injuries associated with stroke and depression

Author

Nicolas Fernandez, Mårten Risling, Johan Davidsson, Caroline Chambon, Béatrice Alescio-Lautier, Michael Ogier, Véronique Paban, Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences intégratives et adaptatives (LNIA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Department of Neuroscience, Karolinska institutet, Stockholm, Sweden, Department of Neuroscience, Karolinska institutet, and Injury Prevention Group, Division of Vehicle Safety, Applied Mechanics, Chalmers University of Technology, Göteborg, Sweden

Subjects
0303 health sciences, Microarray, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Traumatic brain injury, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alcohol dependence, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cognition, Disease, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Frontal lobe, [SCCO.PSYC]Cognitive science/Psychology, medicine, Psychology, Neuroscience, Stroke, 030217 neurology & neurosurgery, Depression (differential diagnoses), 030304 developmental biology
Abstract

International audience; Traumatic brain injury (TBI) is associated with a collection of physical, emotional and cognitive post complications. The background for such complex consequences may be due to a number of different factors, and the nature of these changes indicates that the frontal lobes may be implicated. In this study we have employed gene expression arrays and gene ontology databases to search for possible similarities between different forms of acquired brain injuries in order to test whether molecular relationships exist between the different pathologies. Two types of experimental models for traumatic brain injuries, lateral fluid percussion and rotational acceleration, were used. Their molecular signature was identified and compared with those related to other rodent models simulating stress, depression, alcohol dependence, stroke, and Alzheimer's disease. The data show that the two TBI models share similar gene expression changes with the models with regard to depression and stroke, indicating a common molecular support between these pathologies. The data provided can contribute to the introduction of new treatment strategies related to TBI.

Published
2016

12. Effects of a high-fat–high-fructose diet, stress and cinnamon on central expression of genes related to immune system, hypothalamic–pituitary–adrenocortical axis function and cerebral plasticity in rats – CORRIGENDUM

Author

Nathalie Marissal-Arvy, Cécile Batandier, Julien Dallennes, Frédéric Canini, Laurent Poulet, Karine Couturier, Isabelle Hininger-Favier, Marie-Pierre Moisan, Anne-Marie Roussel, Pierre Mormède, Nutrition et Neurobiologie intégrée, Institut National de la Recherche Agronomique (INRA), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], ANR-07-PNRA-0003,CERVIRMIT,Cerveau, résistance à l'insuline et mitochondrie :Rôle neuroprotecteur des polyphénols de la cannelle dans un modèle animal de syndrome métabolique(2007), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)

Subjects
0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Nutrition and Dietetics, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), 030209 endocrinology & metabolism, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2014

13. Mice gamble for food : individual differences in risky choices and prefrontal cortex serotonin

Author

Françoise Dellu-Hagedorn, Elsa Pittaras, Pierre Serreau, Jessica Bruijel, Sylvie Granon, Jacques Callebert, Arnaud Rabat, Arnaud Cressant, Neurobiologie de la prise de décision, Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, and Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress

Subjects
0303 health sciences, Novelty, Iowa gambling task, Preference, Social relation, Developmental psychology, Task (project management), 03 medical and health sciences, 0302 clinical medicine, medicine, Anxiety, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Serotonin, medicine.symptom, Prefrontal cortex, Psychology, 030217 neurology & neurosurgery, 030304 developmental biology, Cognitive psychology
Abstract

International audience; Background: One of the fundamental questions in Neuroscience is to understand how we choose one option instead of another one when we are in uncertain or ambiguous situation. Some decisions have short- and long-term consequences. The Iowa Gambling Task (IGT) is classically used to study decision-making in humans because it mimics real life situations. By developing a new mice model, we aimed at studying behavioral traits and brain circuits that impact on inter-individual differences in decision making processes.Methods: 72 male C57Bl/6J mice were used to adapt the IGT. We first attempted to adapt the task in operant chambers from rats’ works using long delays as penalties. Our results were not conclusive so we adapted the task to a maze version. Quinine pellets were used as penalties and food pellets as rewards. We also performed behavioral measures of anxiety, novelty exploration, locomotion and social interaction. Finally, we measured levels of monoamines in different brain tissues sampled from the mice subjected to the behavioral task.Results: We show that transferring directly the protocol of the rat’s gambling task to mice using operant conditioning was not successful presumably because of species particularities, such as lower sensitivity to delay penalties. In the maze version, we found that mice exhibited a clear preference for small but safer rewards that allow the maximization of benefits in the long-term. We observed the progressive emergence of inter-individuals differences and specific behavioral and biochemical traits for each subgroup. Namely, risk-prone mice exhibited lower 5-HT level in the prefrontal cortex compared to the others.Conclusion: We were thus able to validate a mouse gambling task and to determine individual profile close to the human and rat results. This study allows us to characterize within a healthy population, subgroups with different behavioral and biochemical profiles.

Published
2013

14. Metyrapone effects on systemic and cerebral energy metabolism

Author

Nadine Fidier, André Peinnequin, Florence Fauvelle, Renaud Maury, Frédéric Canini, Antonia Alonso, Alain Buguet, Cécile Batandier, Jean-Baptiste Drouet, Raymond Cespuglio, Laurent Poulet, Département des environnements opérationnels (IRBA/CRSSA), Institut de Recherche Biomédicale des Armées (IRBA), Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiobiologie et Radiopathologie, Service de Santé des Armées-Ministère de la Défense, Département des Facteurs Humains, Radicaux libres, substrats énergétiques et physeopathologie cérébrale, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Radicaux Libres, Substrats Énergétiques et Physiopathologie Cérébrale, Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France, and Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress

Subjects
Male, medicine.medical_specialty, Transcription, Genetic, [SDV]Life Sciences [q-bio], AMP-Activated Protein Kinases, Biology, Hippocampus, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Prosencephalon, 0302 clinical medicine, Corticosterone, Internal medicine, medicine, Animals, Hippocampus (mythology), HSP70 Heat-Shock Proteins, RNA, Messenger, Enzyme Inhibitors, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, Metyrapone, TOR Serine-Threonine Kinases, Glutamate receptor, Brain, AMPK, Hypothermia, Mitochondria, Rats, 3. Good health, Oxygen, Glutamine, Endocrinology, chemistry, medicine.symptom, Energy Metabolism, 030217 neurology & neurosurgery, Glucocorticoid, medicine.drug
Abstract

Metyrapone is a cytochrome P 450 inhibitor that protects against ischemia- and excitotoxicity-induced brain damages in rodents. This study examines whether metyrapone would act on energy metabolism in a manner congruent with its neuroprotective effect. In a first investigation, the rats instrumented with telemetric devices measuring abdominal temperature, received i.p. injection of either metyrapone or saline. One hour after injection, their blood and hippocampus were sampled. Hippocampus metabolite concentrations were measured using 1 H high-resolution magic angle spinning-magnetic resonance spectroscopy ( 1 H HRMAS-MRS). The hippocampus levels in phosphorylated mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) were measured by Western Blot analysis and those of c-fos and HSP70-2 mRNA were quantified by RT-PCR. In a second investigation, the rats received the same treatment and were sacrificed 1 h after. The functioning of mitochondria was immediately studied on their whole brain. Metyrapone provoked a slight hypothermia which was correlated to the increase in blood glucose concentration. Metyrapone also increased blood lactate concentrations without modifying hippocampus lactate content. In the hippocampus, metyrapone decreased γ-aminobutyric acid (GABA) and glutamate levels but increased glutamine and N-acetyl-aspartate contents (NAA). Phosphorylated mTOR and AMPK and the c-fos and HSP70-2 mRNA levels were similar between treatment groups. Metyrapone did not modify blood corticosterone levels. Mitochondrial oxygen consumption was similar in both groups whatever the substrate used. These metabolic modifications, which take place without modifying blood glucocorticoid levels, are consistent with the neuroprotective properties of metyrapone as demonstrated in animal models.

Published
2012

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