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Immunology, Signal Transduction, and Behavior in Hypothalamic–Pituitary–Adrenal Axis-related Genetic Mouse Models

Authors

  • Susana Silberstein,

    1. Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, and IFYBINE: Instituto de Fisiología, Biología Molecular y Neurociencias–Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
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  • Annette M. Vogl,

    1. Max-Planck Institute of Psychiatry, Munich, Germany
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  • Juán José Bonfiglio,

    1. Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, and IFYBINE: Instituto de Fisiología, Biología Molecular y Neurociencias–Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
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  • Wolfgang Wurst,

    1. Max-Planck Institute of Psychiatry, Munich, Germany
    2. Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
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  • Florian Holsboer,

    1. Max-Planck Institute of Psychiatry, Munich, Germany
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  • Eduardo Arzt,

    1. Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, and IFYBINE: Instituto de Fisiología, Biología Molecular y Neurociencias–Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
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  • Jan M. Deussing,

    1. Max-Planck Institute of Psychiatry, Munich, Germany
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  • Damián Refojo

    1. Max-Planck Institute of Psychiatry, Munich, Germany
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Address for correspondence: Dr. Damian Refojo or Dr. Jan Deussing, Max-Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Voice: +49 (0)89 30622-240; fax: +49 (0)89 30622-610. refojo@mpipsykl.mpg.de; Voice: +49 (0)89 30622-639; fax: +49 (0)89 30622-610. deussing@mpipsykl.mpg.de

Dr. Eduardo Arzt, Laboratorio de Fisiología y Biología Molecular, FCEN, Universidad de Buenos Aires; Ciudad Universitaria, 1428 Buenos Aires, Argentina. Voice: +54-11-4576-3368/86; fax: +54-11-4576-3321. earzt@fbmc.fcen.uba.ar

Abstract

A classical view of the neuroendocrine–immune network assumes bidirectional interactions where pro-inflammatory cytokines influence hypothalamic–pituitary–adrenal (HPA) axis-derived hormones that subsequently affect cytokines in a permanently servo-controlled circle. Nevertheless, this picture has been continuously evolving over the last years as a result of the discovery of redundant expression and extended functions of many of the molecules implicated. Thus, cytokines are not only expressed in cells of the immune system but also in the central nervous system, and many hormones present at hypothalamic–pituitary level are also functionally expressed in the brain as well as in other peripheral organs, including immune cells. Because of this intermingled network of molecules redundantly expressed, the elucidation of the unique roles of HPA axis-related molecules at every level of complexity is one of the major challenges in the field. Genetic engineering in the mouse offers the most convincing method for dissecting in vivo the specific roles of distinct molecules acting in complex networks. Thus, various immunological, behavioral, and signal transduction studies performed with different HPA axis-related mutant mouse lines to delineate the roles of β-endorphin, the type 1 receptor of corticotropin-releasing hormone (CRHR1), and its ligand CRH will be discussed here.

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