Gene expression in the rat brain during prostaglandin D2 and adenosinergically-induced sleep

Authors

  • Akira Terao,

    1. Biosciences Division, SRI International, Menlo Park, California, USA
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    • 1

      The present address of A. Terao is the Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.

    • 3

      These authors contributed equally to the work.

  • Zhi-Li Huang,

    1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka, Japan
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    • 3

      These authors contributed equally to the work.

  • Jonathan P. Wisor,

    1. Biosciences Division, SRI International, Menlo Park, California, USA
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  • Takatoshi Mochizuki,

    1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka, Japan
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    • 2

      The present address of T. Mochizuki is the Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.

  • Dmitry Gerashchenko,

    1. Biosciences Division, SRI International, Menlo Park, California, USA
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  • Yoshihiro Urade,

    1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka, Japan
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  • T. S. Kilduff

    1. Biosciences Division, SRI International, Menlo Park, California, USA
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Address correspondence and reprint requests to Dr Thomas S. Kilduff, Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. E-mail: thomas.kilduff@sri.com

Abstract

Previous studies have supported the hypothesis that macromolecular synthesis occurs in the brain during sleep as a response to prior waking activities and that prostaglandin D2 (PGD2) is an endogenous sleep substance whose effects are dependent on adenosine A2a receptor-mediated signaling. We compared gene expression in the cerebral cortex, basal forebrain, and hypothalamus during PGD2-induced and adenosinergically-induced sleep to results from our previously published study of recovery sleep (RS) after sleep deprivation (SD). Immediate early gene expression in the cortex during sleep induced by PGD2- or by the selective adenosine A2a agonist CGS21680 showed limited similarity to that observed during RS while, in the basal forebrain and hypothalamus, widespread activation of immediate early genes not seen during RS occurred. In all three brain regions, PGD2 and CGS21680 reduced the expression of arc, a transcript whose expression is elevated during SD. Using GeneChips®, the majority of genes induced by either PGD2 or CGS21680 were induced by both, suggesting activation of the same pathways. However, gene expression induced in the brain after PGD2 or CGS21680 treatment was distinct from that described during RS after SD and apparently involves glial cell gene activation and signaling pathways in neural-immune interactions.

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