ポスター
D. 恒常性と神経内分泌システム
D. Homeostatic and Neuroendocrine Systems |
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| 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-002
線虫の温度順化における神経ペプチドを介した腸の脂質貯蔵
Intestinal lipid storage via neuropeptides regulating temperature acclimation in C. elegans
*村上 一寿(1)、本村 晴佳(1)、久原 篤(1)、太田 茜(1)
1. 甲南大学
*Kazutoshi Murakami(1), Haruka Motomura(1), Atsushi Kuhara(1), Akane Ohta(1)
1. Konan University
Keyword: cold tolerance, temperature acclimation, fat metabolism
Cold tolerance in C. elegans is a useful experimental model for understanding molecular and neural systems involved in sensing temperature and in acclimating to environmental temperature changes (Ohta et al., Nature commun, 2014; Okahata et al., Science advances, 2019). Here we show that neuron-gut signaling through neuropeptide controls fat metabolism and fat accumulation in the intestine, which is correlated with past-cultivation temperature dependent cold tolerance. Adipocyte triacylglycerol lipase, ATGL-1, is required for reducing the fat in the intestine. We found that the expression level of ATGL-1::GFP in wild-type animals cultivated at 25°C was higher than that in animals cultivated at 15°C, speculating that amount of fat is lower in the 25°C-cultivated animal than that in the 15°C-cultivated animal. We then used a fat marker, Oil-Red-O, to stain gut-fat in these animals, and found that the lipid storage was actually reduced in 25°C-cultivated wild-type animals comparing to 15°C-cultivated one. As previously reported, brain-gut signaling via neuropeptide activates ATGL-1 promoting lipolysis in the gut, in which FLP-7 (FMRF-type neuropeptide) secreted by head sensory neurons is received by its receptor NPR-22 (GPCR-type neuropeptide receptor) (Palamiuc et al, Nature Commun 2017). We then analyzed the relationship between cultivation temperature-dependent lipid accumulation in the gut and neuropeptide signaling. Both FLP-7 and NPR-22 mutants showed abnormal temperature acclimation and no decrease in the intestinal fat content even at 25°C cultivation. These suggest that FLP-7 and NPR-22 regulate ATGL-1 to modulate the changes in fat mass for acclimation to lower temperatures. We are now investigating the relationship between many molecules involved in temperature acclimation and fat mass, and are trying to understand the coordination between the nervous system and other organs, starting from thermo sensation to fat regulation in the gut. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-003
妊娠ストレス下における母マウスの咀嚼は、仔マウスの海馬におけるミクログリアを介した神経炎症を改善する
Maternal chewing during prenatal stress improves microglia-mediated neuroinflammation in the hippocampus of mouse pups.
*梶本 京子(1)、久田 詠詠(1)、越智 鈴子(1)、津金 裕子(1)、飯沼 光生(1)、東 華岳(2)、久保 金弥(3)
1. 朝日大学歯学部小児歯科、2. 産業医科大学医解剖学、3. 名古屋女子大学大学院生活学研究科
*Kyoko Kajimoto(1), Chie Hisada(1), Ochi Suzuko(1), Hiroko Tsugane(1), Mitsuo Iinuma(1), Kagaku Azuma(2), Kin-ya Kubo(3)
1. Dept Pediatric Dent, Asahi Univ, Sch Dent, Gifu, Japan, 2. UOEH, Med, Ant, Fukuoka, Japan, 3. Grad sch Human Life Sci, Nagoya Women's Univ, Aichi, Japan
Keyword: chewing, Prenatal stress, neuroinflammation, hippocampal
It has been reported that prenatal stress induces elevated levels of the brain inflammatory cytokines, altering the central immune response. Prenatal stress also could disturb the activity of the hypothalamic-pituitary-adrenal axis, leading to increased risk of developing cognitive impairment. Maternal chewing during stress condition ameliorates stress-related cognitive impairment.
In this study, we explored the effects of maternal chewing during prenatal stress condition on the hippocampal microglia-mediated inflammatory responses in the mouse pups. Pregnant mice were divided into CONTROL, STRESS, and STRESS/CHEWING groups. Mice of the STRESS and STRESS/CHEWING groups were subjected to restraint stress from gestational day 12 until parturition. Mice of STRESS/CHEWING group were given a wooden stick to chew on during the period of restraint stress. At weaning, male mice were randomly selected from CONTROL, STRESS, and STRESS/CHEWING groups and assigned to control, stress, or stress/chewing groups, respectively. Four-month-old male pups were administered intraperitoneally with lipopolysaccharide (LPS, 5 mg/kg) or saline vehicle. The plasma corticosterone levels were determined 24 hours after the administration. The mRNA expression levels of the hippocampal inflammatory cytokines were examined and the hippocampal microglia were morphologically analyzed.
Prenatal stress caused significantly increase in the plasma corticosterone level, induced hippocampal microglia priming, and facilitated the release of hippocampal interleukin-1β and tumor necrosis factor-α in mouse pups. Treatment with LPS significantly increased the effects of prenatal stress on the plasma corticosterone level, hippocampal microglial activation, and hippocampal neuroinflammation. Maternal chewing during stress significantly reduced the increase in the plasma corticosterone level, suppressed the microglial hyperactivity, and downregulated inflammatory cytokine levels under basal prenatal stress condition as well as after the administration of LPS.
Our findings suggest that maternal chewing may improve the hippocampal microglia-mediated neuroinflammation induced by prenatal stress and/or LPS administration in mouse pups. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-004
妊娠ストレス下の咀嚼運動が海馬樹状突起に及ぼす影響について
Effects of masticatory movements during prenatal stress on hippocampal dendrites.
*越智 鈴子(1)、吉川 英里(2)、片野 雅久(1)、鈴木 あゆみ(1)、飯沼 光生(1)、東 華岳(3)、久保 金弥(4)
1. 朝日大学歯学部小児歯科、2. 朝日大学歯学部解剖学、3. 産業医科大学医学部解剖学、4. 名古屋女子大学健康科学部
*Suzuko Ochi(1), Eri Yoshikawa(2), Masahisa Katano(1), Ayumi Suzuki(1), Mitsuo Iinuma(1), Kagaku Azuma(3), Kin-ya Kubo(4)
1. Asahi Univ. Dept. Pediatric Dent, Gifu, Japan, 2. Asahi Univ. Dept. Anat, Gifu, Japan, 3. UOEH. Med. Anat, Fukuoka, Japan, 4. Nagoya Women's Univ. Grad. Sch. Human Life Sci, Aichi, Japan
Keyword: prenatal stress, chewing, hippocampal dendrites
Exposure of pregnant females to various psychological stressors is linked with hippocampus-dependent cognitive impairment, abnormal behaviors, and neuropsychiatric disorders in their children. Maternal masticatory movements under stress condition improves stress-induced hippocampal neurogenesis and cognitive deficits in pups. In the present study, we investigated the effects of maternal masticatory movements during restraint stress on the hippocampal neuronal dendrites in mouse pups. Pregnant DDY mice were assigned to control, stress, and stress/chewing groups. Stress mice were subjected to restraint stress for 45 min, 3 times a day (9:00, 12:00, 15:00) from the 12th day of gestation to parturition. Stress/chewing mice were given a wooden stick for chewing during stress period. Control mice were neither exposed to stressor nor given with a stick to chow. Morris water maze test was applied in male mouse pups at 4 months of age. Each mouse received four acquisition trials per day for 7 days. The time from placing the animal into the water until it found the platform was measured as the escape latency. Hippocampal neuronal dendrites were identified in Golgi-Cox stained sections. The results showed that prenatal stress impaired the spatial learning, decreased the number of dendritic branches, total dendritic length, and the spine density in the hippocampal CA1, CA3, and DG regions. Maternal chewing ameliorated prenatal stress-induced cognitive impairment, attenuated the decreased number of dendritic branches, dendritic length, and the spine density in the hippocampal CA1, CA3, and DG regions. Our results indicate that maternal masticatory movements could improve prenatal stress-induced cognitive impairment in mouse pups, at least partially by affecting the hippocampal neuronal dendrites. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-005
ストレスは報酬系異常を介して摂食行動パターンを変化させる
Stress-impaired reward pathway promotes distinct feeding behavior patterns
*藤岡 祐介(1)、河合 香里(1)、勝野 雅央(1)、祖父江 元(2)、石垣 診祐(1,3)
1. 名古屋大学大学院医学系研究科 神経内科学、2. 愛知医科大学、3. 名古屋大学 脳とこころの研究センター
*Yusuke Fujioka(1), Kaori Kawai(1), Masahisa Katsuno(1), Gen Sobue(2), Shinsuke Ishigaki(1,3)
1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2. Aichi Medical University, Nagakute, Japan, 3. Brain and Mind Research Center, Nagoya University, Nagoya, Japan
Keyword: Stress, reward, feeding behavior pattern, VTA
Psychosocial stress can impact feeding behavior outcomes. Although many studies have examined alterations to food intake, little is known about how stress affects feeding behavior patterns. To determine the impact of psychological stress on feeding behavior patterns, mice were subjected to various psychosocial stressors (social isolation, intermittent high-fat-diet, or physical restraint) prior to timed observations in a feeding arena that incorporated multiple bait loci. In addition, in vivo microdialysis was used to assess the effects of stressors on the reward system by measuring dopamine levels in the nucleus accumbens (NAcc) shell. Impaired feeding behavior patterns characterized by significant deviations in bait selection (i.e. fixated feeding) and prolonged periods of eating (i.e. protracted feeding) were observed in stressed mice relative to non-stressed controls. In addition to clear behavioral effects, the stressors also negatively impacted dopamine levels at the nucleus accumbens shell. Normalization of dopamine reversed the fixated feeding behavior, whereas specifically inhibiting neuronal activity in the dopaminergic neurons of the ventral tegmental area that project to the nucleus accumbens shell caused similar impairments in feeding. Given that the deviations were not consistently accompanied by changes in the amount of bait consumed, body weight, or metabolic factors, the qualitative effects of psychosocial stressors on feeding behavior likely reflect perturbations to a critical pathway in the mesolimbic dopamine system. These findings provide compelling evidence that aberrations in feeding behavior patterns can be developed as sensitive biomarkers of psychosocial stress and possibly a prodromal state of neuropsychiatric diseases. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-006
State-Dependant Computation in a Neuron-To-Network Model of the Paraventricular Hypothalamus
*Sam Andrew Mestern(1,2), Aoi Ichiyama(2,3), Gabriel Benigno(3,4), Lyle Muller(3,4,2), Wataru Inoue(2,3)
1. University of Western Ontario, 2. Robarts Research Institute, University of Western Ontario, 3. Brain and Mind Institute, University of Western Ontario, 4. Department of Applied Mathematics, University of Western Ontario
Keyword: Stress, Computational Neuroscience, HPA axis, PVN
The activation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of stress response critical for the maintenance and restoration of homeostasis. Corticotrophin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) forms the apex of the HPA axis, driving the hormonal stress response. These PVN-CRH neurons receive a large variety of synaptic inputs and thus represent a point of primary integration of the signals regulating the activity of the HPA axis. However, how the PVN-CRH neurons function to integrate and transmit stressor signals remains to be determined. [SM1] Recently, our lab utilized in vivo electrophysiology to characterize two distinct firing modes from the PVN-CRH neurons. First, a burst firing mode is characterized by a small burst of spikes followed by a long silence. Second, a tonic mode is characterized by consistent firing. Notably, these distinct firing patterns were not observed spontaneously in ex vivo patch-clamp experiments. We hypothesized that the distinct firing patterns observed might arise from network interactions with the PVN-CRH neurons. Using a computational model of PVN-CRH neurons, we sought to better understand the role of network interactions in this circuit. First, we developed a single neuron adaptive-exponential integrate-and-fire model of PVN-CRH neurons by fitting it to ex vivo patch-clamp data. Next, we implemented this single neuron into a putative recurrent inhibitory network model. Finally, we fit our network parameters to our putative in-vivo CRH neuron recordings. Using our computational approach, we demonstrated that the observed in vivo firing patterns might arise from recurrent communication between PVN-CRH neurons and GABAergic interneurons. Under basal conditions, the recurrent circuit retains the network in the burst firing mode with singular bursts driving long negative inhibitory feedback onto the neurons. We demonstrated that this ‘burst’ mode gates the liability of the PVN-CRH neurons to incoming excitatory input. In contrast, the tonic firing mode increases the sensitivity of PVN-CRH neurons to incoming input. Finally, we demonstrated that injection of the network input into ex vivo PVN-CRH neurons facilitated in vivo-like firing patterns. In summary, our work demonstrates a first-of-its-kind model of PVN-CRH neurons. Furthermore, we demonstrate the potential for state-dependent computation in PVN-CRH neurons using our computational model. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-007
緑の香りが認知的課題中の疲労、作業能率、呼吸循環応答に及ぼす影響
The effects of green odor on fatigue, work efficiency and cardiorespiratory response due to cognitive task
*河合 英理子(1,2)、佐々木 章宏(1)、山野 恵美(1)、岩﨑 美帆(3)、渡辺 恭介(1)、水野 敬(1,3)、渡辺 恭良(1)
1. 理化学研究所 生命機能科学研究センター、2. 日本学術振興会 特別研究員、3. 理化学研究所BDR-ダイキン工業連携センター
*Eriko Kawai(1,2), Akihiro Sasaki(1), Emi Yamano(1), Miho Iwasaki(3), Kyosuke Watanabe(1), Kei Mizuno(1,3), Yasuyoshi Watanabe(1)
1. RIKEN Ctr for Biosystems Dynamics Res, Hyogo, Japan, 2. Japan Soc for the Promotion of Sci, Tokyo, Japan, 3. RIKEN BDR - DAIKIN collab Ctr, Hyogo, Japan
Keyword: Aromatherapy, Fatigue, Work efficiency
Aromatherapy is one of the most familiar treatments for fatigue and stress. A green odor reminiscent of new leaves is known to prevent from increased fatigue and decreased work efficiency. Here, we investigated the anti-fatigue effect of a green odor in terms of subjective evaluation, cognitive performance, cardiorespiratory responses and autonomic nerve activity (ANA). A total of twenty-three healthy individuals (13 males and 10 females, 33.9 ± 9.2 years old) participated in two-day experiment. Subjects performed fatigue-inducing task (1-back and 2-back tasks) for 30 minutes and rested for 10 minutes before and after the task (baseline and recovery periods, respectively). During the task and rest periods, electrocardiogram for measuring heart rate (HR) and ANA, beat-to-beat blood pressure (BP) and respiratory variables were recorded. On one of the two days, the subjects inhaled odorless air during baseline period and green-odor air during fatigue-induced and recovery periods. On the other day, they inhaled odorless air during all periods. Subjective evaluation including fatigue and stress, and sensory evaluation including comfort of green-odor and odorless airs were measured using visual analogue scale (VAS) at before, intermediate and after fatigue-induced periods. We analyzed the data from 12 subjects who felt more comfortable for green-odor air than for odorless air since uncomfortable odor could induce stress irrelevant to fatigue inducing task. We found sensory evaluation of the green odor increased after odor inhalation from baseline, indicating that the green odor was perceived. The VAS score for fatigue increased after fatigue-inducing task both in green-odor and odorless air, but the increase was smaller for green-odor air than for odorless air. The correct rate for the 1-back task maintained from initial to last of the task (95.7% and 95.8%, respectively) in green-odor air, but significantly decreased from 97.7% to 91.4% in odorless air. Whereas in the group of subjects who felt uncomfortable with the green odor, no such difference was observed. HR, BP, and respiratory rate acutely increased at the start of the task, but the increase level was less in green-odor air than in odorless air. These results suggest that the comfortable green odor has an anti-fatigue effect that inhibits increased fatigue and decreased work efficiency, as well as an effect that suppresses elevated tension and consequently, increased HR and respiratory rate. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-008
養育行動の発達において特定の養育者は必須ではない
The absence of a specific caregiver is not essential for the development of maternal behavior in mice.
*今井 早希(1)、牛谷内 真子(1)、川上 誉紘(1)
1. 東海大学
*Saki Imai(1), Mako Ushiyachi(1), Yoshihiro Kawakami(1)
1. Tokai University
Keyword: Maternal behavior, Early-life stress, Animal model, Attachment disorder
Disruptions of mother-infant relationship, such as abuse, neglect, and loss of parents, affect development and behavior of offspring. The early-life stress has long-lasting effects and increases later risk for psychiatric disorders. Maternal care important for securing nutrition, regulating temperature, and accepting stimulation (the sense of touch, olfaction, and hearing) of infants. Infant and young child must continuous relationship with the parent or primary caregiver for physical and psychological development. However, it is unknown that the importance of the “specific” caregiver for development. The level of maternal care is transmitted to their pups and proper maternal behaviors in a cross-fostering experiment using mice. The aim of present study was to evaluate the effect the specific caregiver on maternal behavior in female mice. For this purpose, we use a repeated cross-foster (RCF) model in mice. RCF pups were separated from their biological mothers after birth and rotated to some lactating females repeatedly until weaning (PD25), whereas Handling pups experienced short separations (15min./day) from biological mother at same periods. RCF pups gave same time of maternal care between PD1-14 compared Handling pups. There were no significant differences in the level of maternal behaviors after parturition, the nest building, the survival percentage rate of pups, and the weight of pups. These findings suggest that the absence of a specific caregiver is not essential for the development of maternal behavior in mice. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-009
An Inhibitory Network Controls the Activity of Stress-Responsive Neurons in the Paraventricular Nucleus of the Hypothalamus
*Aoi Ichiyama(1), Samuel Mestern(2), Gabriel Benigno(3), Kaela Scott(4), Brian Allman(5), Lyle Muller(6), Wataru Inoue(7)
1. Grad Neuroscience, Schulich Sch of Med and Dent, Univ of Western Ontario, London, Canada, 2. Grad Neuroscience, Schulich Sch of Med and Dent, Univ of Western Ontario, London, Canada, 3. Brain and Mind Inst, Dept App Math, Univ of Western Ontario, London, Canada, 4. Dept Anat Cell Biol, Schulich Sch of Med and Dent, Univ of Western Ontario, London Canada, 5. Dept Anat Cell Biol, Schulich Sch of Med and Dent, Univ of Western Ontario, London Canada, 6. Brain and Mind Inst, Dept App Math, Univ of Western Ontario, London, Canada, 7. Robarts Research Inst, Dept Phys Pharm, Schulich Sch of Med and Dent, Univ of Western Ontario, London Canada
Keyword: stress, PVN, CRH, electrophysiology
Corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are a key node of stress information processing that drives the neuroendocrine response via activity-dependent release of CRH into the blood. However, very little is known about the single-cell firing properties of PVN-CRH neurons in vivo that regulates this hormone output.
We used a combination of optogenetics and electrophysiology to “tag” the in vivo firing activity of CRH neurons by expressing light-activated channelrhodopsin (ChR2). In anesthetized, head-fixed mice, we first recorded the spontaneous single-unit firing activities of PVN neurons during a no-stress baseline, and subsequently with sciatic nerve stimulation (stress stimulus). In the same mice, light-induced, short-latency single unit activity from ChR2-expressing CRH neurons was recorded. The latter recording provided fingerprint waveforms of light-responding PVN-CRH neurons, allowing us to identify the activity of PVN-CRH neurons from spontaneous recordings using offline analysis.
Light-responsive PVN-CRH single unit activities were recorded (n = 18). These “identified” units revealed that PVN-CRH neurons fire in two modes – rhythmic brief bursts (2-5 trains at >100 Hz) and single-spike firing (tonic firing with variable frequencies). These rhythmic bursts have long (~1s) inter-burst intervals that constrain the average firing rate of the cell while single spiking is permissive for higher firing activities. Our computational (spiking network) model shows that the firing patterns can be generated by recurrent CRH-GABA interactions. In biological PVN-CRH neurons ex vivo, the injection of whole-cell currents derived from our computational model recreates the in vivo-like switch between rhythmic brief bursts and single spiking, providing a direct evidence that physiologically relevant network inputs enable rapid change in the firing patterns. The circuit model was further pharmacologically tested in vivo via local antagonism of GABAA receptors. Both in vivo, ex vivo and in silico data show that the switch from rhythmic bursting to single spiking underlie stress-induced high-activity state which may be relevant for hormone release. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3P-010
運動は分子シャペロン含有の血漿由来エクソソーム分泌を亢進する
Physical exercise increases the secretion of molecular chaperone-containing extracellular vesicles circulating in blood
*武田 明子(1,2)、武内 敏秀(1,2)、皆川 栄子(3)、和田 圭司(3)、永井 義隆(1,2)
1. 大阪大学大学院医学系研究科 神経難病認知症探索治療学、2. 近畿大学医学部 脳神経内科学、3. 国立精神・神経医療研究センター 神経研究所 疾病研究第4部
*Akiko Takeda(1,2), Toshihide Takeuchi(1,2), Eiko N Minakawa(3), Keji Wada(3), Yoshitaka Nagai(1,2)
1. Dept. Neurotherapeutics, Grad. Sch. Med., Osaka Univ., Osaka, Japan, 2. Dept. Neurology, Fac. Med., Kindai Univ, Osaka, Japan, 3. Dept. Degenerative Neurological Diseases, Natl. Inst. Neurosci., NCNP, Tokyo, Japan
Keyword: Alzheimer’s disease, Exercise, Extracellular vesicles, Molecular chaperone
Alzheimer’s disease (AD), one of the neurodegenerative diseases, is thought to be caused by aggregation and aberrant accumulation of disease-causative proteins including amyloid β. Although epidemiological studies have shown that physical exercise reduces risk for onset of AD, the molecular mechanisms remain unclear. Recent research in humans suggests that physical exercise can increase the number of extracellular vesicles (EVs) circulating in blood. We previously reported that exosomes, one of the EVs, mediate cell-to-cell transmission of molecular chaperones, leading to suppression of neurodegeneration in Drosophila models. Therefore, we hypothesize that physical exercise-induced circulating EVs contribute to the reduced risk for AD.
In this study, to reveal the effect of physical exercise on EV secretion and contents, we examined the particle size, concentration and cargo molecules in plasma EVs from mice after physical exercise. Blood was collected from mice that were subjected to treadmill exercise, and plasma EVs including exosomes were isolated by ultracentrifugation. To investigate the change of particle diameter and number in plasma EVs following physical exercise, nanoparticle tracking analysis was performed. We found that the increase in the number of EVs was observed at 30 min after physical exercise, but not at 24 hrs, indicating that physical exercise induces transient increase in the number of EVs circulating in blood. On the other hand, there was no difference in the diameter of EVs. Proteome analysis of plasma EVs revealed that physical exercise altered the protein contents in circulating EVs. In particular, we showed that the levels of molecular chaperones such as heat shock proteins in EVs were increased by physical exercise. Interestingly, these increased levels of molecular chaperones in EVs after physical exercise were attenuated by administration of an exosomal inhibitor, demonstrating that physical exercise induces the secretion of molecular chaperone-containing EVs into circulation.
Taken together, our data demonstrate that physical exercise increases the number of EVs circulating in blood and changes their contents, which might contribute to the reduced risk for AD. | | | |
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