title: Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice.
abstract: Sleep apnea (SA) causes not only sleep disturbances, but also neurocognitive impairments and/or psychoemotional disorders. Here, we studied the effects of intermittent hypoxia (IH) on forebrain Fos expression using obese diabetic db/db mice to explore the pathophysiological alterations in neural activities and the brain regions related to SA syndrome. Male db/db mice were exposed to IH stimuli (repetitive 6-min cycles of 1min with 5% oxygen followed by 5min with 21% oxygen) for 8h (80 cycles) per day or normoxic condition (control group) for 14 days. Fos protein expression was immunohistochemically examined a day after the last IH exposure. Mapping analysis revealed a significant reduction of Fos expression by IH in limbic and paralimbic structures, including the cingulate and piriform cortices, the core part of the nucleus accumbens and most parts of the amygdala (i.e., the basolateral and basomedial amygdaloid nuclei, cortical amygdaloid area and medial amygdaloid nucleus). In the brain stem regions, Fos expression was region-specifically reduced in the ventral tegmental area while other regions including the striatum, thalamus and hypothalamus, were relatively resistant against IH. In addition, db/db mice exposed to IH showed a trend of sedative and/or depressive behavioral signs in the open field and forced swim tests. The present results illustrate that SA in the obese diabetic model causes neural suppression preferentially in the limbic and paralimbic regions, which may be related to the neuropsychological disturbances associated with SA.
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nagao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishioka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Saki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Asuka
authors.initials: A
authors.lastname: Ono
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sakagami
authors.forename: Sho
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ueda
authors.forename: Madoka
authors.initials: M
authors.lastname: Hara
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokudome
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ohno
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008032:Limbic System / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012891:Sleep Apnea Syndromes / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Fos expression; IH; Intermittent hypoxia; Limbic system; SA; Sleep apnea; db/db mice; intermittent hypoxia; sleep apnea