ストレス Stress
P1-1-167 一過性全脳虚血後の皮質再構築のポテンシャル変化とストレス曝露による影響 Acute stress exposure preceding transient global brain ischemia decreases cortical remodeling potential in the rat cingulate cortex ○朽名伸夫1, 後藤公聖1, 江里口隆1, 大島秀規1, 山下晶子2, 須磨健1, 酒谷薫3, 山本隆允3, 吉野篤緒1, 片山容一1 ○Nobuo Kutsuna1, Kosei Goto1, Takashi Eriguchi1, Hideki Oshima1, Akiko Yamashita2, Takeshi Suma1, Kaoru Sakatani3, Takamitsu Yamamoto3, Atsuo Yoshino1, Yoichi Katayama1 日本大学医学部脳神経外科1, 日本大学医学部脳神経外科学系応用システム神経科学分野2, 日本大学工学部次世代工学技術研究センター3 Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine1, Division of Applied System Neuroscience, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan2, NEWCAT Institute, Department of Electrical and Electronics Engineering, Nihon University College of Engineering, Koriyama, Japan3 Doublecortin (DCX)-expressing cells are candidates that play key roles in the adult cortical remodeling. We have reported the number of DCX-expressing cells per unit area decreases after stress exposure or global brain ischemia (GBI) in the rat cingulate cortex. The aim of present study is to investigate whether the decrease in DCX-expressing cells is accelerated after GBI by preconditioning with acute stress exposure. Eighteen rats were divided into 3 groups; acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by forced swim paradigm or bilateral common carotid artery occlusion, respectively. DCX-expressing cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-expressing cells decreased after GBI with or without stress preconditioning in the ACC and RS (ANOVA followed by Tukey-type test, P < 0.001). Moreover the number of DCX-expressing cells in Group P decreased to a greater degree significantly than that in Group G (P < 0.05). Most of DCX-expressing cells were co-localized with GABAergic neuronal marker, parvalbumin. The present study indicates that cortical remodeling potential in the cingulate GABAergic neurons decreases after GBI, moreover, thus the ratio of decrease is accelerated by an acute stress preconditioning.	P1-1-168 視床下部室傍核ニューロンによるストレス性c-Fos発現に及ぼす局所的な低温刺激提示の影響 The effect of locally applied low thermal stimulus on stress-induced c-Fos expression by paraventricular neurons of rats ○山下賢也1, 長友亘1, 杉本皓司1, 首藤文洋1, 久野節二1 ○Kenya Yamashita1, Wataru Nagatomo1, Koji Sugimoto1, Fumihiro Shutoh1, Setsuji Hisano1 筑波大院・人間・感性認知脳科学1 Lab.Systems Brain Sciences, Kansei Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki1 The aim of this study is to investigate an effect of the local thermal stimulation on restraint stress-induced c-Fos expression in the paraventricular nucleus (PVN) of rats. Adult male Sprague-Dawley rats were restrained for 30 min in a transparent plastic tube, while their forelimb pads touching (group L, n=6) or not (group S, n=6) to an aluminium block (10C°) cooled with a thermocontroller in an incubator (35C°). Two hours after the start of restraint, the rats were transcardially perfusion-fixed with a modified Zamboni's fixative. The hypothalamus was dissected out, paraffin-embedded, cut into serial coronal sections (5 μm-thick), and immunostained for c-Fos. The PVN regions were photographed and neurons having a c-Fos-stained nucleus were automatically counted in the whole PVN and in 4 different subnuclei using Image J. Data were statistically compared between both animal groups. The number of c-Fos-stained neurons in the whole PVN was significantly smaller (p<0.05) in group L than in group S. In particular, the numbers of c-Fos-stained neurons in the posterior magnocellular and the ventral part of the medial parvocellular subregions were smaller (p<0.05) in group L than in group S, showing significant attenuation of neuronal c-Fos expression. However, no significant difference was found in the dorsal parvocellular and the dorsal part of medial parvocellular subregions between groups L and S. These data suggest that a local thermal stimulation for forelimbs has an inhibitory effect on the restraint stress-induced activation of PVN neurons, with representing the subnucleus-related functional diversity.
P1-1-169 反復社会挫折ストレスによる情動変容における自然免疫関連分子の役割 A role for the innate immune signaling in emotional changes caused by repeated social defeat stress in mice ○北岡志保1, 聶翔1, 田中昂平1, 井本有基2, 瀬木-西田恵里3, 古屋敷智之1, 成宮周1 ○Shiho Kitaoka1, Xiang Nie1, Kohei Tanaka1, Yuuki Imoto2, Eri Segi-Nishida3, Tomoyuki Furuyashiki1, Shuh Narumiya1 京都大院・医・神経細胞薬理1, 京都大院・薬・生体情報制御学分野2, 京都大院・薬・システム創薬科学3 Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto1, Department of Physiological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences2, Department of Systems Bioscience for Drug Discovery, Kyoto University Graduate School of Pharmaceutical Sciences3 Repeated or excessive exposure to stress cause emotional changes, such as depressive behavior and elevated anxiety. Several groups including ours reported that repeated stress elevates a marker for microglial activation and induces the morphological change of microglia. We also showed that COX-1, a prostaglandin synthase enriched in microglia, is required for social avoidance induced by repeated social defeat stress. Whereas these lines of evidence implicate microglia in emotional changes caused by repeated stress, the nature of microglial response to repeated stress and its molecular mechanism remain unknown. To address this issue, we have established a method of rapidly isolating microglia from the brains of stressed mice for gene expression profiling, and have found that repeated stress increases the mRNA levels of damage-associated molecules that activate the innate immune system, in microglia as well as other cell types in the brain. Consistent with a role for the innate immune signaling in repeated stress, mice deficient in MyD88, an adaptor molecule critical for the innate immune signaling, fail to show social avoidance induced by repeated stress. Furthermore, immunofluorescent staining showed that MyD88 is selectively expressed in microglia and endothelial cells in the brain. We are paving the way for identifying a role for the innate immune signaling in these cell types in emotional changes caused by repeated stress.	P1-1-170 母胎ストレス中のチューイングは脳由来神経成長因子の発現障害を改善する Chewing during prenatal stress ameliorates stress-induced suppression of brain-derived neurotrophic factor expression in the hippocampus ○久保金弥1, 大西見佳2, 村林知香2, 飯沼光生2, 森大輔3, 東華岳4, 小野塚實5 ○Kin-ya Kubo1, Mika Onishi2, Chika Murabayashi2, Mitsuo Iinuma2, Daisuke Mori3, Chen Huayue4, Minoru Onozuka5 星城大学大学院健康支援学研究科1, 朝日大学歯学部小児歯科学分野2, 朝日大学歯学部補綴学分野3, 岐阜大学大学院医学研究科4, 日体柔整専門学校5 Seijoh Univ. Grad. Sch. Health Care Studies1, Dept. Pediatric Dent., Asahi Univ. Sch. Dent.2, Dept. Prosthodontics., Asahi Univ. Sch. Dent.3, Gifu Univ. Grad. Sch. Medicine4, Nittai Jusei Medical Coll. For Therapeutics5 Maternal stress induces learning impairment and suppresses cell proliferation in the hippocampal dentate gyrus in pups. We previously reported that maternal chewing during prenatal stress rescues the stress-induced decreases in hippocampal neurogenesis and cognitive impairment in pups. Learning affects hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression, and BDNF affects neurogenesis. Here we analyzed the expression levels of BDNF protein using Western blot analysis, neurogenesis, and learning ability in pups. Pregnant mice were exposed to restraint stress beginning on day 15 and continuing until delivery. Half of the dams were given a wooden stick to chew on during restraint stress. The pups were raised to adulthood and learning ability, neurogenesis, and BDNF expression were analyzed. Restraint stress during pregnancy inhibited cell proliferation and BDNF protein expression in the hippocampus, and impaired learning ability, but, maternal chewing improved the restraint stress-induced suppression of cell proliferation, BDNF protein expression, and learning ability. These findings suggest that maternal chewing ameliorates the maternal stress-induced suppression of BDNF in the hippocampus, which in turn reduces the cognitive impairment and decreased in hippocampal neurogenesis in the pups.
P1-1-171 みどりの香りの反復提示は遅延性恐怖条件付けによる行動反応の長期的変容に対してパロキセチン様の緩和作用を示す Repeated green odor exposure and chronic paroxetine treatment attenuate long-term behavioral alterations induced by delay fear conditioning in rats ○二階堂義和1, 山田順子2, 右田啓介2, 柴祐子2, 中島敏博3, 上野伸哉2 ○Yoshikazu Nikaido1, Junko Yamada2, Keisuke Migita2, Yuko Shiba2, Toshihiro Nakashima3, Shinya Ueno2 弘前大学院・医1, 弘前大院・医・脳神経生理学2, 京工繊大・応用生物・生体機能学3 Hirosaki Univ. Grad. Sch. Med., Hirosaki, Japan1, Dept. Neurophysiol., Hirosaki Univ. Grad. Sch. Med., Hirosaki, Japan2, Dept. Appl. Biol., Kyoto Inst. of Tech., Kyoto, Japan3 Our previous researches demonstrate that green odor (GO), a mixture of cis-3-hexenol and trans-2-hexenal, attenuates acute fear, anxiety and stress responses to psychological stressors; however, it is still unknown whether GO affects long-lasting stress associated with behavioral alterations. In the present study, we investigated the effects of GO and paroxetine, a selective serotonin reuptake inhibitor, on long-term fear, anxiety, sensorimotor gating and depressive-like responses in rats subjected to delay fear conditioning. Two weeks after delay fear conditioning with a tone stimulus, animals showed increased freezing response to conditioned stimulus. These animals also displayed anxiety behaviors in novel environment, enhanced prepulse inhibition of the acoustic startle response and increased depressive-like behaviors in the forced swim test. In contrast, rats administrated with paroxetine (1.0 mg/kg/day i.p.) during 2 weeks after fear conditioning exhibited attenuations of these stress-induced behavioral alterations. Similarly, conditioned animals treated by daily 0.03 % GO exposures (200 μl, 60 min/day) during 2 weeks showed alleviations of long-lasting conditioned fear response, anxiety in novel environment and enhanced acoustic prepulse inhibition, but not depressive-like responses in the forced swim test. These results suggest that repeated GO exposure might facilitate the extinction of long-term fear memory and reduce the accompanying anxiety and abnormal sensorimotor gating like chronic paroxetine treatment, except for depression-related behaviors.	P1-1-172 幼弱期慢性ストレス付加によるバレル皮質シナプス可塑性変化の分子メカニズムの解明 Neonatal chronic stress alters actin dynamics and experience-driven synaptic plasticity via ADF/cofilin inactivation in the rat barrel cortex ○多田敬典1, 須山紅美子1, 高橋琢哉1 ○Hirobumi Tada1, Kumiko Suyama1, Takuya Takahashi1 横浜市立大学医学部生理学1 Dept Physiol, Yokohama City Univ, Yokohama1 Experience-dependent neural plasticity is crucial for the establishment of neural circuits and cognitive functions. Abnormal environment early in life such as neonatal chronic stress could cause various psychiatric disorders by the disruption of circuit formation. However, the mechanisms underlying how early long-lasting stress alters circuit organization remain poorly understood. Here, we found that neonatal chronic stress with social isolation phosphorylated and inactivated ADF/cofilin, the actin depolymerizing factor, via the stress glucocorticoid hormone signaling in the increase of immobilized fraction of actin. This led to the prevention of experience-driven synaptic AMPA receptor delivery in the developing rat barrel cortex. Thus, neonatal chronic stress inactivates ADF/cofilin, alters actin dynamics, and results in the blockade of experience-driven synaptic AMPA receptor delivery in the sensory cortex, leading to the malfunctioning in sensory processing which constitutes prominent symptoms in psychiatric disorders.
P1-1-173 老化と慢性ストレス状態の脳内ストレス応答関連領域における神経活動 Neural activity of the stress response areas in aged and chronic stressed mice brain ○船上仁範1, 宮本朋佳1, 飯田拓真1, 阪井邦正1, 岸本茉希1, 谷口友梨1, 豊田和1, 大浦沙貴子1, 岡部由季1, 和田哲幸1, 長野護2, 重吉康史2, 市田成志1 ○Yoshinori Funakami1, Tomoyoshi Miyamoto1, Takuma Iida1, Kunimasa Sakai1, Maki Kishimoto1, Yuri Taniguchi1, Kazu Toyoda1, Sakiko Ohura1, Yuki Okabe1, Tetsuyuki Wada1, Mamoru Nagano2, Yasufumi Shigeyoshi22, Seiji Ichida1 近畿大・薬・生化学1, 近畿大・医・解剖学2 Division of Biochemistry, Kinki University Faculty of Parmacy, Osaka1, Deptment of Anatomy and Neurobiology, Faculty of Medicine, Kinki University, Osaka2 The body copes with every stress from the ambient by performing a stress response and maintains homeostasis. We examined a neural activity of thalamus, hypothalamus, pons and medulla oblongata by acute stress to investigate relationship of aging and chronic stress. Male ddY mice weighing 20-25 g were used and bred for 4-5 (young mice), 60 and 100 weeks (aged mice) at room temperature (24 ± 1°C) under a 12 h-light and dark cycle (lights on at 8:00 am) and allowed to eat and drink freely tap water. Acute stress indicates the condition of 4°C exposure for 1 hour, while Chronic stress indicates SART stress loading ,as follows. Mice were transferred between 24°C room's cage and 4°C room's cage hourly from 9:00 to 16:00 and housed in a cage at 4°C from l6:00 to 09:00 the following morning. This procedure was repeated for 8 days up to 11:30 on the day of the each experiment. Neural activity was counted the number of c-Fos immuno-reactive (c-Fos-IR) cells. In young and aged mice, the number of c-Fos-ir cells in paraventricular thalamic nucleus, paraventricular hypothalamic nucleus (PVN), dorsomedial hypothalamic nucleus, lateral parabrachial nucleus and raphe pallidus nucleus (RPa) were increased by acute stress. A number of c-Fos-ir cells in PVN and RPa of 100 weeks aged mice were significantly decreased by acute stress. However, that in 5 areas of SART-stressed mice was not changed by acute stress. Repeating three times of acute stress, the increase of c-Fos-ir cells's number was gradually decreased in young mice, but this change was not found in aged mice. These results suggest that aged and chronic stressed mice decrease the stress responses through the hypothalamus-pituitary-adrenal axis that started from PVN by acute stress. In aging, it may be hard to occur a habituation for stress caused by repeated acute stress.

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