一般口演
ストレス / 神経内分泌など
Stress / Neuroendocrine System
座長：櫻井 武（筑波大学医学医療系） |
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| 2022年6月30日 10:00～10:15 沖縄コンベンションセンター 会議場A2 第7会場
1O07m2-01
BALB/cマウスにおける長期間の社会的敗北ストレスがその後の社会的接触の際の脳活動へ与える影響 ―新規な半自動c-Fosマッピング法を用いた解析―
Effect of chronic social defeat stress on brain activity during social interaction in BALB/c mice using a novel semi-automated c-Fos mapping method
*岡村 響(1,2)、安垣 進之助(1,3)、荒井 佳史(1,4)、櫻井 勝康(1)、柳沢 正史(1)、滝沢 穂高(5)、林 悠(1,6)
1. 筑波大学国際統合睡眠医科学研究機構（WPI-IIIS）、2. 筑波大学グローバル教育院ヒューマニクス学位プログラム、3. 筑波大学大学院人間総合科学研究科生命システム医学専攻、4. 筑波大学大学院人間総合科学学術院フロンティア医科学学位プログラム、5. 筑波大学システム情報系情報工学域、6. 京都大学大学院医学研究科
*Hibiki Okamura(1,2), Shinnosuke Yasugaki(1,3), Yoshifumi Arai(1,4), Katsuyasu Sakurai(1), Masashi Yanagisawa(1), Hotaka Takizawa(5), Yu Hayashi(1,6)
1. International Institute for Integrative Sleep Medicine (WPI-IIIS), Univ. of Tsukuba, 2. Ph. D. Prog in Humanics, SIGMA, Univ. of Tsukuba, 3. Doc Prog in Biomed Sci, Grad Sch of Comprehensive Human Sci, Univ. of Tsukuba, 4. Master’s Prog in Med Sci, Grad Sch of Comprehensive Human Sci, Univ. of Tsukuba, 5. Fac of Eng, Inf and Sys, Univ. of Tsukuba, 6. Dept of Human Health Sci, Grad Sch of Med, Kyoto Univ
Keyword: Stress, Depression, Mouse, Behavior
In humans, chronic stress is a major factor of depression. Patients with depression show loss of interest, increased anxiety, hopeless feelings, changes in body weight, and sleep disorders. Mice also show similar phenotypes following chronic stress. Elucidating the mechanisms responsible for the emergence of these stress-induced phenotypes in mice is expected to contribute to the understanding of the neural mechanism of depression in humans. Social defeat stress (SDS) is one of the methods to apply chronic stress to mice (Golden et al., Nat Protoc, 2011; Nie et al., Neuron, 2018). Notably, about half of the mice that are exposed to chronic SDS show social avoidance (avoidant mice), whereas the remaining mice do not (non-avoidant mice) (Krishnan V et al., Sci Rep, 2018; Higashida et al., Sci Rep, 2018). Understanding the mechanisms underlying the segregation into these two subpopulations may provide important clues to understanding individual differences in stress resilience. In this study, we aimed to identify brain regions whose activity during social interaction are different between mice that underwent chronic SDS and naïve mice, or between avoidant mice and non-avoidant mice. We first investigated how chronic SDS affects BALB/c mice, a strain that shows higher stress susceptibility compared to the widely used C57BL/6 mice (Razzoli et al., Behav Brain Res, 2011; Tsuchimine et al., Biochem Biophys Res Commun, 2020; Ishikawa et al., Br J Pharmacol, 2021). We found that BALB/c mice that were exposed to seven days of SDS showed phenotypes including increased social avoidance, and the effects remained even 2 weeks after the end of stress exposure. Interestingly, whether each individual mouse exposed to chronic SDS belongs to the avoidant group or the non-avoidant group was not fixed over the 2 weeks. To investigate the activity of neurons in each brain region following social interaction, we used c-Fos mapping. c-Fos is one of the markers for neuronal activity. To this end, we established a novel method to conduct whole-brain c-Fos mapping based on semi-automated image processing. Comprehensive analysis of c-Fos expression revealed that in defeated mice, several brain regions exhibit c-Fos signals that are different from naïve mice. Moreover, c-Fos signals in several brain regions were different between avoidant mice and non-avoidant mice. These results contribute to understanding how prior social stress affects the brain activity during social interaction and provide a novel method for efficient c-Fos mapping across various brain regions. | | 2022年6月30日 10:15～10:30 沖縄コンベンションセンター 会議場A2 第7会場
1O07m2-02
社会的敗北ストレスによって誘導される行動変容における前頭前皮質オキシトシン受容体発現ニューロンの生理機能
Oxytocin receptor-expressing neurons in the medial prefrontal cortex modulate stress responses induced by social defeat
*犬束 歩(1)、向井 康敬(2)、吉田 匡秀(1)、高柳 友紀(1)、山中 章弘(2)、尾仲 達史(1)
1. 自治医科大学医学部生理学講座、2. 名古屋大学環境医学研究所
*Ayumu Inutsuka(1), Yasutaka Mukai(2), Masahide Yoshida(1), Yuki Takayanagi(1), Akihiro Yamanaka(2), Tatsushi Onaka(1)
1. Dept Physiol, Jichi Medical University, 2. Res Inst Environ Med, Nagoya University
Keyword: oxytocin, stress, prefrontal cortex, nanobody
The hypothalamus plays an important role in stress response. Oxytocin-producing neurons localized in the hypothalamus are strongly activated by social defeat stress, but their physiological functions are still unclear. We focused on the function of the oxytocin receptor (Oxtr) in the medial prefrontal cortex (mPFC). First, we selectively knocked out Oxtr in the prefrontal cortex of Oxtr-flox mice by local administration of an adeno-associated virus (AAV) vector expressing Cre recombinase. Selective ablation of Oxtr in the mPFC exacerbated social avoidance induced by chronic social defeat stress. Second, axonal projections from Oxtr-expressing neurons in the mPFC were selectively visualized by administration of AAV vectors expressing GFP-dependent Cre and Cre-dependent tdTomato in the prefrontal cortex of Oxtr-Venus mice. We found that Oxtr-expressing neurons in the mPFC include not only somatostatin-positive interneurons but also projection neurons that extend axons to the basolateral amygdala. Third, we injected AAV vectors expressing YC-nano, a fluorescent calcium indicator, into the mPFC of Oxtr-Cre mice and performed calcium imaging of brain sections. Transient increase of calcium concentration in response to oxytocin was observed in Oxtr-expressing cells in the mPFC. Fourth, we administered AAV vectors expressing hM3Dq to the mPFC of Oxtr-Cre mice and manipulated neuronal activity. The mice treated with CNO during the process of social defeat stress showed a diminished increase in immobility time in the forced swimming test after chronic social defeat stress. These results suggest that activity of Oxtr-expressing neurons in the mPFC moderates the behavioral changes induced by social defeat stress. | | 2022年6月30日 10:30～10:45 沖縄コンベンションセンター 会議場A2 第7会場
1O07m2-03
雄ラット扁桃体内側核後背側部のガストリン放出ペプチド系における性行動調節メカニズム
The gastrin-releasing peptide receptor system in the posterodorsal part of the medial amygdala controls sexual activity and sexual preference in male rats
*大坪 秋人(1)、上田 涼太(1)、高松 廉(1)、大野 智輝(1)、前嶋 翔(1)、越智 拓海(1,2)、坂本 竜哉(1)、坂本 浩隆(1)
1. 岡山大学理学部附属臨海実験所/共同利用拠点、2. 神奈川大学理学部生物科学科
*Akito Otubo(1), Ryota Ueda(1), Ren Takamatsu(1), Tomoki Ono(1), Sho Maejima(1), Takumi Oti(1,2), Tatsuya Sakamoto(1), Hirotaka Sakamoto(1)
1. Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan, 2. Department of Biological Sciences, Faculty of Science, Kanagawa University, Kanagawa, Japan
Keyword: SEXUAL BEHAVIOR, THE GASTRIN-RELEASING PEPTIDE RECEPTOR , MEDIAL AMYGDALA
Sexual behavior in male rats is induced by the reception of pheromones. The posterodorsal part of the medial amygdala (MePD) is known to be responsible for pheromone reception in rats. We focused on the gastrin-releasing peptide receptor (GRPR) system in the brain controlling male sexual activity, and found that a collection of GRPR-expressing neurons in the MePD (MePDGRPR neurons) is activated by sexual behavior. However, it is unclear how MePDGRPR neurons regulate male sexual activity. In this study, we analyzed the function of MePDGRPR neurons using transgenic rats in which human diphtheria toxin receptor and red fluorescent protein genes were inserted downstream of the GRPR promoter. First, we analyzed whether MePDGRPR neurons are activated during sexual behavior by using the expression of c-Fos, a neural activation marker, as an index. As a result, the expression of c-Fos was significantly increased in MePDGRPR neurons specifically by ejaculation, suggesting that MePDGRPR neurons are involved in ejaculation. Furthermore, using the target cell knockout method mediated by human diphtheria toxin receptor, we examined the effect of specific disruption of MePDGRPR neurons on male sexual activity by using both sexual behavior and olfactory sexual preference tests. These results showed that specific lesion of MePDGRPR neurons significantly decreased the number of ejaculations and also prolonged the latency to the first ejaculation. Furthermore, loss of MePDGRPR neurons in males attenuated the preference to estrus females. These results suggest that MePDGRPR neurons play an important role in both ejaculatory function and sexual preference in male rats via the GRPR-mediated mechanism. | | 2022年6月30日 10:45～11:00 沖縄コンベンションセンター 会議場A2 第7会場
1O07m2-04
視床下部における腹内側核PACAPから背内側核ガラニンへの神経ペプチドシグナルによる摂食制御機構の解明
Regulation of feeding by neuropeptide signaling from ventromedial-PACAP to dorsomedial-galanin in the hypothalamus
*神戸 悠輝(1)、グエン タン チュン(1)、新谷 紀人(2)、橋本 均(2,3,4,5,6)、栗原 崇(1)、宮田 篤郎(1)
1. 鹿児島大院・医歯学総合・薬理、2. 大阪大・院薬・神経薬理、3. 大阪大・連合小児、4. 大阪大・データビリティフロンティア機構、5. 大阪大・先導的学際研究機構、6. 大阪大・院医・分子医薬
*Yuki Kambe(1), Trung Thanh Nguyen(1), Norihito Shintani(2), Hitoshi Hashimoto(2,3,4,5,6), Takashi Kurihara(1), Atsuro Miyata(1)
1. Dept. Pharmacol., Grad. Sch. Med. Dent. Sci., Kagoshima Univ., 2. Lab. Mol. Neuropharmacol., Grad. Sch. Pharmaceut. Sci., Osaka Univ., 3. United Grad. Sch. Child Dev., Osaka Univ., 4. Div. Biosci., Inst. Datability Sci., Osaka Univ., 5. Open Transdisciplinary Res. Initiatives, Osaka Univ., 6. Dept. Mol. Pharm. Sci., Grad. Sch. Med., Osaka Univ.
Keyword: Appetite, Hypothalamus, Pituitary adenylate cyclase-activating polypeptide, Galanin
We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) in the ventromedial hypothalamic nucleus (VMH) enhances feeding at night and after fasting and inhibits feeding during the day. On the other hand, galanin is also a neuropeptide highly expressed in the hypothalamus and has been reported to be involved in feeding regulation. In this study, we investigated the involvement of VMH-PACAP to the dorsomedial hypothalamic nucleus (DMH)-galanin signaling in the regulation of feeding. The expression of galanin in the hypothalamus was significantly increased by fasting, but this increase was canceled in PACAP knockout mice. Furthermore, overexpression of PACAP in the VMH increased galanin expression, while knockdown of PACAP in the VMH decreased the expression of galanin, indicating that the expression of galanin in the hypothalamus might be regulated by PACAP in the VMH. Therefore, we expressed synaptophysin-EGFP chimeric protein in PACAP neurons in the VMH and visualized the neural projection to the hypothalamic region where galanin was highly expressed. A strong EGFP signal was observed in the DMH, indicating that PACAP-expressing cells of the VMH projected to the DMH. Furthermore, immunostaining of galanin in the DMH showed that galanin expression increased with fasting, but this was not observed in PACAP knockout mice. When galanin in the DMH was knocked down, food intake at night and after fasting was decreased, and food intake during the day was increased, as in PACAP knockout mice. These results indicated that galanin in the DMH may regulate feeding downstream of PACAP in the VMH. | |
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