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Developmental plasticity of the carotid chemoafferent pathway in rats that are hypoxic during the prenatal period

Authors

  • J. Peyronnet,

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
    2. Université Paul Cézanne Aix-Marseille III, UMR CNRS 6153, Physiologie Neurovégétative, Avenue Escadrille Normandie Niemen, cedex 13397, Marseille, France
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  • J. C. Roux,

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
    2. INSERM U491, Université de la Méditerranée Aix-Marseille II, Génétique médicale et développement, Faculté de Médecine de la Timone, Marseille, France
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  • J. Mamet,

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
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  • D. Perrin,

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
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  • J. Lachuer,

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
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  • J. M. Pequignot,

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
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  • Y. Dalmaz

    1. Université Lyon 1, UMR CNRS 5123, Physiologie intégrative Cellulaire et Moléculaire, Villeurbanne, F-69622, Lyon, France
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Dr J. Peyronnet-Roux, as above.2
E-mail: j.peyronnet-roux@univ-cezanne.fr

Abstract

The chemoreflex pathway undergoes postnatal maturation, and the perinatal environment plays a critical role in shaping respiratory control system. We investigated the role of prenatal hypoxia on the maturation of the chemoreflex neural circuits regulating ventilation in rat. Effects of hypoxia (10% O2) from the 5th to the 20th day of gestation were studied on male offspring at birth and on postnatal days 3, 7, 21 and 68. Maturation of the respiratory control system was assessed by in vivo tyrosine hydroxylase (TH) activity measurement in peripheral chemoreceptors (carotid bodies, petrosal ganglia), and in brainstem catecholaminergic cell groups (A2C2c and A1C1 areas in the medulla, A5 and A6 areas in the pons). Resting ventilation and ventilatory response to hypoxia were evaluated as functional sequelae. In peripheral structures, prenatal hypoxia reduced TH activity within the first postnatal week and enhanced it later. In contrast, in central areas, prenatal hypoxia upregulated TH activity within the first postnatal week and downregulated it later. The in vivo TH activity impairment is therefore tissue specific, with an opposite effect on the peripheral and central neural circuits. A shift of the effect of prenatal hypoxia occurred between 1 and 3 weeks, indicating a postnatal temporal effect of prenatal hypoxia. An important period in the development of the chemoafferent pathway occurred between the first and the third postnatal week. Functionally, prenatal hypoxia impaired resting ventilation and ventilatory response to hypoxia. The alterations of the catecholaminergic components of the chemoafferent pathway resulting from prenatal hypoxia might contribute to impair postnatal respiratory behaviour.

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