title: Effects of arundic acid, an astrocytic modulator, on the cerebral and respiratory functions in severe hypoxia.
abstract: Mild hypoxia increases ventilation, but severe hypoxia depresses it. The mechanism of hypoxic ventilatory depression, in particular, the functional role of the cerebrum, is not fully understood. Recent progress in glial physiology has provided evidence that astrocytes play active roles in information processing in various brain functions. We investigated the hypothesis that astrocytic activation is necessary to maintain the cerebral function and ventilation in hypoxia, by examining the responses of EEG and ventilation to severe hypoxia before and after administration of a modulator of astrocytic function, arundic acid, in unanesthetized mice. Ventilatory parameters were measured by whole body plethysmography. When hypoxic ventilatory depression occurred, gamma frequency band of EEG was suppressed. Arundic acid further suppressed ventilation, and the EEG power was suppressed in a dose-dependent manner. Arundic acid also suppressed hypoxia-induced c-Fos expression in the hypothalamus. We conclude that severe hypoxia suppresses the cerebral function which could reduce the stimulus to the brainstem resulting in ventilatory depression. Astrocytic activation in hypoxia may counteract both cerebral and ventilatory suppression.
authors.affiliation: Department of Biomedical Engineering, Graduate School of Science and Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan; Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Isato
authors.initials: I
authors.lastname: Fukushi
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan; Fujita Memorial Nanakuri Institute, Fujita Health University, 423 Oodori-cho, Tsu, Mie 514-1296, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Anatomy and Morphological Neuroscience, Shimane University School of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan.
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan; Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokawato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hasebe
authors.affiliation: Institute of Socio-Arts and Sciences, The University of Tokushima, 1-1 Minamijosanjima-cho, Tokushima 770-8502, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan; Public Higher Medical Professional School in Opole, 68 Katowicka Street, Opole 45-060, Poland.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Pokorski
authors.affiliation: Department of Biomedical Engineering, Graduate School of Science and Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Jouji
authors.initials: J
authors.lastname: Horiuchi
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Electronic address: yasumasaokada@1979.jukuin.keio.ac.jp.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002210:Caprylates / Q000494:pharmacology*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000069280:Electrocorticography; D065818:Gamma Rhythm / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D010993:Plethysmography, Whole Body; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012119:Respiration / Q000187:drug effects*
chemical_list: D002210:Caprylates; D002491:Central Nervous System Agents; C459360:ONO2506; D016760:Proto-Oncogene Proteins c-fos
keywords: Arundic acid; EEG; Glia; Hypothalamus; Hypoxic ventilatory depression; Respiratory control