Researchers Database

yoshida masahide

    DivisionofBrainandNeurophysiology,DepartmentofPhysiology Research Associate
Last Updated :2021/11/23

Researcher Information

URL

Research funding number

  • 30533955

J-Global ID

Research Interests

  • stress   social behavior   vasopressin   Oxytocin   Prolactin releasing peptide   

Research Areas

  • Life sciences / Physiology

Academic & Professional Experience

  • 2014  Jichi Medical UniversitySchool of Medicine助教

Education

  • 2005/04 - 2008/03  日本学術振興会 特別研究員(DC1)
  • 2005/04 - 2008/03  東北大学大学院  農学研究科  応用生命科学専攻博士課程
  • 2003/04 - 2005/03  東北大学大学院  農学研究科  応用生命科学専攻修士課程
  • 1999/04 - 2003/03  Tohoku University  Faculty of Agriculture  Department of Applied Biological Chemistry

Association Memberships

  • JAPAN SOCIETY FOR BIOSICENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY   THE MOLECULAR BIOLOGY SOCIETY OF JAPAN   THE JAPAN NEUROSCIENCE SOCIETY   Japan Neuroendocrine Society   

Published Papers

  • Naoki Usui, Masahide Yoshida, Yuki Takayanagi, Naranbat Nasanbuyan, Ayumu Inutsuka, Hiroshi Kurosu, Hiroaki Mizukami, Yoshiyuki Mori, Makoto Kuro-O, Tatsushi Onaka
    Journal of neuroendocrinology e13026  2021/08 [Refereed]
     
    Fibroblast growth factor 21 (FGF21) modulates energy metabolism and neuroendocrine stress responses. FGF21 synthesis is increased after environmental or metabolic challenges. Detailed roles of FGF21 in the control of behavioural disturbances under stressful conditions remain to be clarified. Here, we examined the roles of FGF21 in the control of behavioural changes after social defeat stress in male rodents. Central administration of FGF21 increased the number of tyrosine hydroxylase-positive catecholaminergic cells expressing c-Fos protein, an activity marker of neurones, in the nucleus tractus solitarius and area postrema. Double in situ hybridisation showed that some catecholaminergic neurones in the dorsal medulla oblongata expressed β-Klotho, an essential co-receptor for FGF21, in male mice. Social defeat stress increased FGF21 concentrations in the plasma of male mice. FGF21-deficient male mice showed social avoidance in a social avoidance test with C57BL/6J mice (background strain of FGF21-deficient mice) and augmented immobility behaviour in a forced swimming test after social defeat stress. On the other hand, overexpression of FGF21 by adeno-associated virus vectors did not significantly change behaviours either in wild-type male mice or FGF21-deficient male mice. The present data are consistent with the view that endogenous FGF21, possibly during the developmental period, has an inhibitory action on stress-induced depression-like behaviour in male rodents.
  • Makiya Matsumoto, Masahide Yoshida, Buddhini Wimarsha Jayathilake, Ayumu Inutsuka, Katsuhiko Nishimori, Yuki Takayanagi, Tatsushi Onaka
    Journal of Neuroendocrinology 14 (33) e12980  0953-8194 2021/05 [Refereed]
  • Shota Okabe, Yuki Takayanagi, Masahide Yoshida, Tatsushi Onaka
    Scientific Reports 11 (1) 3805 - 3805 2021/02 [Refereed][Not invited]
     
    AbstractGentle touch contributes to affiliative interactions. We investigated the effects of gentle stroking in female rats on the development of affiliative behaviors toward humans and we exploratively examined brain regions in which activity was influenced by stroking. Rats that had received stroking stimuli repeatedly after weaning emitted 50-kHz calls, an index of positive emotion, and showed affiliative behaviors toward the experimenter. Hypothalamic paraventricular oxytocin neurons were activated in the rats after stroking. The septohypothalamic nucleus (SHy) in the post-weaningly stroked rats showed decreased activity in response to stroking stimuli compared with that in the non-stroked control group. There were negative correlations of neural activity in hypothalamic regions including the SHy with the number of 50-kHz calls. These findings revealed that post-weaning stroking induces an affiliative relationship between female rats and humans, possibly via activation of oxytocin neurons and suppression of the activity of hypothalamic neurons.
  • Conditional ablation of vasopressin-synthesizing neurons in transgenic rats
    Jun Watanabe, Yuki Takayanagi, Masahide Yoshida, Tatsuya Hattori, Michiko Saito, Kenji Kohno, Eiji Kobayashi, Tatsushi Onaka
    Journal of Neuroendocrinology 2021 [Refereed]
  • 尾仲 達史, Nasanbuyan Naranbat, Jayathilake Buddhini Wimarsha, 吉田 匡秀, 高柳 友紀, 犬束 歩
    日本内分泌学会雑誌 (一社)日本内分泌学会 96 (1) 133 - 133 0029-0661 2020/08
  • Gentle stroking stimuli induce affiliative responsiveness to humans in male rats
    Shota Okabe, Yuki Takayanagi, Masahide Yoshida, Tatsushi Onaka
    Scientific reports 10 (1) 9135  2020/06 [Refereed][Not invited]
  • 吉田 匡秀, 高柳 友紀, 木村 正, 西森 克彦
    日本内分泌学会雑誌 (一社)日本内分泌学会 95 (4) 1458 - 1458 0029-0661 2020/02
  • Toshihiro Nakano, Kazuhiro Shiizaki, Yutaka Miura, Masahiro Matsui, Keisei Kosaki, Shoya Mori, Kunihiro Yamagata, Seiji Maeda, Takuya Kishi, Naoki Usui, Masahide Yoshida, Tatsushi Onaka, Hiroaki Mizukami, Ruri Kaneda, Kazunori Karasawa, Kosaku Nitta, Hiroshi Kurosu, Makoto Kuro-O
    Scientific reports 9 (1) 19247 - 19247 2019/12 [Refereed][Not invited]
     
    Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21-/- mice died earlier than wild-type mice. Paradoxically, these Fgf21-/- CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21-/- CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.
  • Yoshida M, Takayanagi Y, Ichino-Yamashita A, Sato K, Sugimoto Y, Kimura T, Nishimori K
    Endocrinology 160 (12) 2800 - 2810 2019/12 [Refereed][Not invited]
  • Noriyuki Akahoshi, Hiroki Handa, Rintaro Takemoto, Shotaro Kamata, Masahide Yoshida, Tatsushi Onaka, Isao Ishii
    International journal of molecular sciences 20 (14) 3507  2019/07 [Refereed][Not invited]
     
    Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia-a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine γ-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia/homocysteinemia. We investigated whether Cth-deficient (Cth-/-) pregnant mice display any features of preeclampsia. Cth-/- females developed normally but showed mild hypertension (~10 mmHg systolic blood pressure elevation) in late pregnancy and mild proteinuria throughout development/pregnancy. Cth-/- dams had normal numbers of pups and exhibited normal maternal behavior except slightly lower breastfeeding activity. However, half of them could not raise their pups owing to defective lactation; they could produce/store the first milk in their mammary glands but not often provide milk to their pups after the first ejection. The serum oxytocin levels and oxytocin receptor expression in the mammary glands were comparable between wild-type and Cth-/- dams, but the contraction responses of mammary gland myoepithelial cells to oxytocin were significantly lower in Cth-/- dams. The contraction responses to oxytocin were lower in uteruses isolated from Cth-/- mice. Our results suggest that elevated homocysteine or other unknown factors in preeclampsia-like Cth-/- dams interfere with oxytocin that regulates milk ejection reflex.
  • Naranbat Nasanbuyan, Masahide Yoshida, Yuki Takayanagi, Ayumu Inutsuka, Katsuhiko Nishimori, Akihiro Yamanaka, Tatsushi Onaka
    Endocrinology 159 (2) 763 - 775 2018/02 [Refereed][Not invited]
     
    Social stress has deteriorating effects on various psychiatric diseases. In animal models, exposure to socially dominant conspecifics (i.e., social defeat stress) evokes a species-specific defeat posture via unknown mechanisms. Oxytocin neurons have been shown to be activated by stressful stimuli and to have prosocial and anxiolytic actions. The roles of oxytocin during social defeat stress remain unclear. Expression of c-Fos, a marker of neuronal activation, in oxytocin neurons and in oxytocin receptor‒expressing neurons was investigated in mice. The projection of oxytocin neurons was examined with an anterograde viral tracer, which induces selective expression of membrane-targeted palmitoylated green fluorescent protein in oxytocin neurons. Defensive behaviors during double exposure to social defeat stress in oxytocin receptor‒deficient mice were analyzed. After social defeat stress, expression of c-Fos protein was increased in oxytocin neurons of the bed nucleus of the stria terminalis, supraoptic nucleus, and paraventricular hypothalamic nucleus. Expression of c-Fos protein was also increased in oxytocin receptor‒expressing neurons of brain regions, including the ventrolateral part of the ventromedial hypothalamus and ventrolateral periaqueductal gray. Projecting fibers from paraventricular hypothalamic oxytocin neurons were found in the ventrolateral part of the ventromedial hypothalamus and in the ventrolateral periaqueductal gray. Oxytocin receptor‒deficient mice showed reduced defeat posture during the second social defeat stress. These findings suggest that social defeat stress activates oxytocin-oxytocin receptor systems, and the findings are consistent with the view that activation of the oxytocin receptor in brain regions, including the ventrolateral part of the ventromedial hypothalamus and the ventrolateral periaqueductal gray, facilitates social defeat posture.
  • Yuki Takayanagi, Masahide Yoshida, Akihide Takashima, Keiko Takanami, Shoma Yoshida, Katsuhiko Nishimori, Ichiko Nishijima, Hirotaka Sakamoto, Takanori Yamagata, Tatsushi Onaka
    Biological psychiatry 81 (3) 243 - 251 2017/02 [Refereed][Not invited]
     
    BACKGROUND: Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. METHODS: Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. RESULTS: Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. CONCLUSIONS: The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits.
  • Shota Okabe, Masahide Yoshida, Yuki Takayanagi, Tatsushi Onaka
    Neuroscience letters 600 22 - 7 2015/07 [Refereed][Not invited]
     
    Gentle touching or stroking has anxiolytic actions and contributes to the establishment of an intimate relationship between individuals. Oxytocin administration also has anxiolytic actions and facilitates social behaviors. In this study, we examined effects of stroking stimuli on activation of oxytocin neurons and emission of 50-kHz ultrasonic vocalizations, an index of positive emotion, in rats. The number of oxytocin neurons expressing Fos protein was increased in the hypothalamus, especially in the dorsal zone of the medial parvicellular part of the paraventricular nucleus. The number of 50-kHz ultrasonic vocalizations was also increased. These findings suggest that pleasant sensory stimuli activate hypothalamic oxytocin neurons.
  • Nishimori K, Sato K, Hidema S, Yoshida M, Mizukami H
    Interdisciplinary Information Sciences 21 (3) 283 - 288 2015 [Refereed][Not invited]
  • Onaka T, Okabe S, Takayanagi Y, Yoshida M
    Interdisciplinary Information Sciences 21 (3) 189 - 195 2015 [Refereed][Not invited]
  • Masahide Yoshida, Yuki Takayanagi, Tatsushi Onaka
    Endocrinology 155 (8) 2996 - 3004 2014/08 [Refereed][Not invited]
     
    Fear responses play evolutionarily beneficial roles, although excessive fear memory can induce inappropriate fear expression observed in posttraumatic stress disorder, panic disorder, and phobia. To understand the neural machineries that underlie these disorders, it is important to clarify the neural pathways of fear responses. Contextual conditioned fear induces freezing behavior and neuroendocrine responses. Considerable evidence indicates that the central amygdala plays an essential role in expression of freezing behavior after contextual conditioned fear. On the other hand, mechanisms of neuroendocrine responses remain to be clarified. The medial amygdala (MeA), which is activated after contextual conditioned fear, was lesioned bilaterally by infusion of N-methyl-d-aspartate after training of fear conditioning. Plasma oxytocin, ACTH, and prolactin concentrations were significantly increased after contextual conditioned fear in sham-lesioned rats. In MeA-lesioned rats, these neuroendocrine responses but not freezing behavior were significantly impaired compared with those in sham-lesioned rats. In contrast, the magnitudes of neuroendocrine responses after exposure to novel environmental stimuli were not significantly different in MeA-lesioned rats and sham-lesioned rats. Contextual conditioned fear activated prolactin-releasing peptide (PrRP)-synthesizing neurons in the medulla oblongata. In MeA-lesioned rats, the percentage of PrRP-synthesizing neurons activated after contextual conditioned fear was significantly decreased. Furthermore, neuroendocrine responses after contextual conditioned fear disappeared in PrRP-deficient mice. Our findings suggest that the MeA-medullary PrRP-synthesizing neuron pathway plays an important role in neuroendocrine responses to contextual conditioned fear.
  • M. Yamashita, Y. Takayanagi, M. Yoshida, K. Nishimori, M. Kusama, T. Onaka
    JOURNAL OF NEUROENDOCRINOLOGY 25 (5) 455 - 465 0953-8194 2013/05 [Refereed][Not invited]
     
    Food intake activates neurones expressing prolactin-releasing peptide (PrRP) in the medulla oblongata and oxytocin neurones in the hypothalamus. Both PrRP and oxytocin have been shown to have an anorexic action. In the present study, we investigated whether the activation of oxytocin neurones following food intake is mediated by PrRP. We first examined the expression of PrRP receptors (also known as GPR10) in rats. Immunoreactivity of PrRP receptors was observed in oxytocin neurones and in vasopressin neurones in the paraventricular and supraoptic nuclei of the hypothalamus and in the bed nucleus of the stria terminalis. Application of PrRP to isolated supraoptic nuclei facilitated the release of oxytocin and vasopressin. In mice, re-feeding increased the expression of Fos protein in oxytocin neurones of the hypothalamus and bed nucleus of the stria terminalis. The increased expression of Fos protein in oxytocin neurones following re-feeding or i.p. administration of cholecystokinin octapeptide (CCK), a peripheral satiety factor, was impaired in PrRP-deficient mice. CCK-induced oxytocin increase in plasma was also impaired in PrRP-deficient mice. Furthermore, oxytocin receptor-deficient mice showed an increased meal size, as reported in PrRP-deficient mice and in CCKA receptor-deficient mice. These findings suggest that PrRP mediates, at least in part, the activation of oxytocin neurones in response to food intake, and that the CCKPrRPoxytocin pathway plays an important role in the control of the termination of each meal.
  • Takeshi Y Hiyama, Masahide Yoshida, Masahito Matsumoto, Ryoko Suzuki, Takashi Matsuda, Eiji Watanabe, Masaharu Noda
    Cell metabolism 17 (4) 507 - 19 1550-4131 2013/04 [Refereed][Not invited]
     
    Salt homeostasis is essential to survival, but brain mechanisms for salt-intake control have not been fully elucidated. Here, we found that the sensitivity of Na(x) channels to [Na(+)](o) is dose-dependently enhanced by endothelin-3 (ET-3). Na(x) channels began to open when [Na(+)](o) exceeded ~150 mM without ET-3, but opened fully at a physiological [Na(+)](o) (135–145 mM) with 1 nM ET-3. Importantly, ET-3 was expressed in the subfornical organ (SFO) along with Nax, and the level was robustly increased by dehydration. Pharmacological experiments revealed that endothelin receptor B (ET(B)R) signaling is involved in this modulation of Na(x) gating through protein kinase C and ERK1/2 activation. ET(B)R agonists increased the firing rate of GABAergic neurons via lactate in the SFO, and an ET(B)R antagonist attenuated salt aversion during dehydration. These results indicate that ET-3 expression in the SFO is tightly coupled with body-fluid homeostasis through modulation of the [Na(+)](o) sensitivity of Na(x).
  • T. Onaka, Y. Takayanagi, M. Yoshida
    JOURNAL OF NEUROENDOCRINOLOGY 24 (4) 587 - 598 0953-8194 2012/04 [Refereed][Not invited]
     
    Oxytocin neurones are activated by stressful stimuli, food intake and social attachment. Activation of oxytocin neurones in response to stressful stimuli or food intake is mediated, at least in part, by noradrenaline/prolactin-releasing peptide (PrRP) neurones in the nucleus tractus solitarius, whereas oxytocin neurones are activated after social stimuli via medial amygdala neurones. Activation of oxytocin neurones induces the release of oxytocin not only from their axon terminals, but also from their dendrites. Oxytocin acts locally where released or diffuses and acts on remote oxytocin receptors widely distributed within the brain, resulting in anxiolytic, anorexic and pro-social actions. The action sites of oxytocin appear to be multiple. Oxytocin shows anxiolytic actions, at least in part, via serotoninergic neurones in the median raphe nucleus, has anorexic actions via pro-opiomelanocortin neurones in the nucleus tractus solitarius and facilitates social recognition via the medial amygdala. Stress, obesity and social isolation are major risk factors for mortality in humans. Thus, the oxytocinoxytocin receptor system is a therapeutic target for the promotion of human health.
  • Ludovic Wrobel, Ara Schorscher-Petcu, Anouk Dupre, Masahide Yoshida, Katsuhiko Nishimori, Eliane Tribollet
    NEUROSCIENCE LETTERS 495 (1) 49 - 54 0304-3940 2011/05 [Refereed][Not invited]
     
    Oxytocin can influence various spinal functions. However, little is known about the spinal neuronal networks responsible for oxytocin effects. The aim of this study was to localize and characterize spinal neurons expressing oxytocin receptors. We used an oxytocin receptor-reporter mouse in which the fluorescent protein Venus is expressed under the control of the oxytocin receptor gene promoter. At all segmental levels. Venus-expressing neurons were most numerous in the substantia gelatinosa, mingled with protein kinase C gamma interneurons in the innermost layer of the inner lamina II, which, in contrast to the outer two thirds of this layer, does not receive nociceptive input. Venus-expressing neurons were also observed in the intermediolateral and sacral parasympathetic nuclei, where they represented about 5% of presumed preganglionic neurons identified by choline acetyltransferase immunoreactivity. Finally. Venus immunoreactivity was detected in lumbar and sacral dorsal gray commissures as well as in isolated neurons scattered in different regions of the dorsal horn. Altogether, our results establish the location of neurons putatively involved in oxytocin modulation of spinal functions, in particular of sexual functioning and nociception. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Michael S. Sinclair, Isabel Perea-Martinez, Gennady Dvoryanchikov, Masahide Yoshida, Katsuhiko Nishimori, Stephen D. Roper, Nirupa Chaudhari
    PLOS ONE 5 (8) e11980  1932-6203 2010/08 [Refereed][Not invited]
     
    Background: The neuropeptide, oxytocin (OXT), acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout) overconsume salty and sweet (i.e. sucrose, saccharin) solutions. We asked if OXT might also act on taste buds via its receptor, OXTR. Methodology/Principal Findings: Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I) taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca(2+) imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca(2+)](i) mobilization in a subset of taste cells (EC(50) similar to 33 nM). OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II) nor Presynaptic (Type III) cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene. Conclusions/Significance: We conclude that OXT elicits Ca(2+) signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I) taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I) taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of appetite regulation that employ circulating homeostatic and satiety signals.
  • Masahide Yoshida, Yuki Takayanagi, Kiyoshi Inoue, Tadashi Kimura, Larry J. Young, Tatsushi Onaka, Katsuhiko Nishimori
    JOURNAL OF NEUROSCIENCE 29 (7) 2259 - 2271 0270-6474 2009/02 [Refereed][Not invited]
     
    The oxytocin receptor has been implicated in the regulation of reproductive physiology as well as social and emotional behaviors. The neurochemical mechanisms by which oxytocin receptor modulates social and emotional behavior remains elusive, in part because of a lack of sensitive and selective antibodies for cellular localization. To more precisely characterize oxytocin receptor-expressing neurons within the brain, we generated an oxytocin receptor-reporter mouse in which part of the oxytocin receptor gene was replaced with Venus cDNA (a variant of yellow fluorescent protein). Examination of the Venus expression revealed that, in the raphe nuclei, about one-half of tryptophan hydroxylase-immunoreactive neurons were positive for Venus, suggesting a potential role for oxytocin in the modulation of serotonin release. Oxytocin infusion facilitated serotonin release within the median raphe nucleus and reduced anxiety-related behavior. Infusion of a 5-HT(2A/2C) receptor antagonist blocked the anxiolytic effect of oxytocin, suggesting that oxytocin receptor activation in serotonergic neurons mediates the anxiolytic effects of oxytocin. This is the first demonstration that oxytocin may regulate serotonin release and exert anxiolytic effects via direct activation of oxytocin receptor expressed in serotonergic neurons of the raphe nuclei. These results also have important implications for psychiatric disorders such as autism and depression in which both the oxytocin and serotonin systems have been implicated.
  • Masaki Kawamata, Masahide Yoshida, Yukihiko Sugimoto, Tadashi Kimura, Yutaka Tonomura, Yuki Takayanagi, Teruyuki Yanagisawa, Katsuhiko Nishimori
    MOLECULAR AND CELLULAR ENDOCRINOLOGY 283 (1-2) 32 - 37 0303-7207 2008/02 [Refereed][Not invited]
     
    The dramatic increase of oxytocin (OT) receptor (OTR) in the myometrium as well as circulating progesterone withdrawal has been thought to be the most important factor in the induction and accomplishment of parturition since delivery fails in prostaglandin F-2 alpha receptor (FP) knockout (FP KO) mice. The expression levels of OTR mRNA/protein were not dramatically increased in the near-term uteri of FP KO mice. However, OT-induced myometrial contractions and the concentration-response curves in FP KO in vitro were almost similar to those in wild-type (WT) mice. OT-infusion (0.3 U/day) enabled FP KO mice to experience successful delivery, and furthermore the duration until the onset was hastened by a higher dose of OT (3 U/day). The plasma progesterone levels of FP KO females were maintained at high levels, but decreased during labor by OT-infusion Q U/day). These results suggest that OT has potentials to induce strong myometrial contractions in uterus with low expression levels of OTR and luteolysis in ovary, which enabled Fl? KO females to undergo successful delivery. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Katsuhiko Nishimori, Yuki Takayanagi, Masahide Yoshida, Yoshiyuki Kasahara, Larry J. Young, Masaki Kawamata
    ADVANCES IN VASOPRESSIN AND OXYTOCIN: FROM GENES TO BEHAVIOUR TO DISEASE 170 79 - 90 0079-6123 2008 [Refereed][Not invited]
     
    To further define the function of the oxytocin receptor (OXTR) in vivo, we generated mice deficient in the Oxtr gene (Oxtr-/-). Oxtr-/- mice had no obvious deficits in fertility or sexual behaviour, but displayed several aberrations in social behaviours, including male aggression, and mother-offspring interaction. In addition, they showed novel physiological defects including obesity, and dysfunction in body temperature control when exposed to cold. We review here our new findings with Oxtr-/- mice, and introduce newly generated Oxtr-Venus knockin mice as a potential tool for examining molecular physiology of Oxtr-neurons.
  • Y Takayanagi, M Yoshida, IF Bielsky, HE Ross, M Kawamata, T Onaka, T Yanagisawa, T Kimura, MM Matzuk, LJ Young, K Nishimori
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 102 (44) 16096 - 16101 0027-8424 2005/11 [Refereed][Not invited]
     
    The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr(-/-)) and compared them with OXT-deficient (Oxt(-/-)) mice. Oxtr(-/-) mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr(-/-) dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr(-/-) males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr(-/-) males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt(-/-) males from Oxt(-/-) dams, but not from Oxt(+/-) dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.

Conference Activities & Talks

  • Facilitation of social defeat posture by oxytocin/oxytocin receptor systems  [Invited]
    Masahide Yoshida, Naranbat Nasanbuyan, Tatsushi Onaka
    The 43rd Annual Meeting of the Japan Neuroscience Society  2020/07
  • The role of oxytocin in behavioral changes induced by social defeat stress  [Invited]
    Ayumu Inutsuka, Masahide Yoshida, Yuki Takayanagi, Tatsushi Onaka(
    The 97th Annual Meeting of the Physiological Society of Japan
  • 分娩に必要な子宮収縮因子の機能的なヒエラルキー  [Not invited]
    Yoshida M, Takayanagi Y, Kimura T, Nishimori K
    The 46th Annual meeting of Japan neuroendocrine society  2019/10
  • Roles of oxytocin in responses to social defeat stress  [Invited]
    高柳 友紀, Naranbat Nasanbuyan, 吉田 匡秀, 犬束 歩, 尾仲 達史
    第92回日本内分泌学会学術総会  2019/05
  • Genetic manipulation of oxytocin receptor-expressing neurons using GFPdependent Cre recombinase and Oxtr-Venus knock-in mice.  [Not invited]
    Inutsuka A, Yoshida M, Takayanagi Y, Onaka T
    13th World Congress on Neurohypophysial Hormones (WCNH2019)  2019/04
  • Genetic evidence that oxytocin/oxytocin receptor system is crucial to induce enough labor force for appropriate expulsion of the fetus in mice.  [Not invited]
    Yoshida M, Takayanagi Y, Kimura T, Nishimori K
    13th World Congress on Neurohypophysial Hormones (WCNH2019)  2019/04
  • Indispensable role of the oxytocin receptor for allogrooming behavior toward socially distressed cage mates in female mice.  [Not invited]
    Yoshida M, Matsumoto M, Okabe S, Inutsuka A, Yuki Takayanagi Y, Onaka T
    13th World Congress on Neurohypophysial Hormones (WCNH2019)  2019/04
  • The oxytocin-oxytocin receptor system in stress-related pathways.  [Invited]
    Onaka T, Yoshida M, Matsumoto M, Nasanbuyan N, Takayanagi Y, Inutsuka A
    The Third Sino-Japan Symposium on the Frontier of Behavioral Neuroendocrinology  2019/03
  • 前頭前皮質に局在するオキシトシン受容体発現ニューロンのストレス応答における機能解析  [Not invited]
    犬束歩, 吉田匡秀, 高柳友紀, 尾仲達史
    第46回自律神経生理研究会  2018/12
  • Oxytocin-Oxytocin receptor systems facilitate social defeat posture in male mice.  [Not invited]
    Nasanbuyan N, Yoshida M, Takayanagi Y, Inutsuka A, Nishimori K, Yamanaka A, Onaka T
    第41回日本神経科学大会  2018/07
  • Roles of Oxytocin in the Control of stress and social behavior.  [Invited]
    Onaka T, Takayanagi Y, Yoshida M, Nasanbuyan N, Okabe S, Inutsuka A
    9th International Congress of Neuroendocrinology in Toronto  2018/07
  • Allo-grooming behavior to distressed cagemate mice: activation of oxytocin receptor expressing cells.  [Not invited]
    Matsumoto M, Yoshida M, Inutuka A, Takayanagi Y, Onaka T
    第95回日本生理学会大会  2018/03
  • Toward the elucidation of the mechanism of affiliative relationship among interspecific species.  [Not invited]
    Okabe S, Takayanagi Y, Yoshida M, Onaka T
    第95回日本生理学会大会  2018/03
  • オキシトシン/オキシトシン受容体系と個体の集団への適応性  [Not invited]
    吉田匡秀, Naranbat Nasanbuyan, 高柳友紀, 松本まきや, 岡部祥太, 犬束歩, 尾仲達史
    .新学術領域研究「共感性の進化・神経基盤」第2回若手研究者合宿  2018/02
  • 中枢神経系におけるオキシトシン投射線維とオキシトシン受容体の分布:新規の社会行動関連神経回路とその機能  [Not invited]
    吉田匡秀, Naranbat Nasanbuyan, 高柳友紀, 犬束歩, 尾仲達史
    第28回バゾプレシン研究会  2018/01
  • 社会的敗北とオキシトシン  [Not invited]
    尾仲達史, Naranbat Nasanbuyan, 吉田匡秀, 高柳友紀, 犬束歩
    第27回日本行動神経内分泌研究会  2017/04
  • Transgene expression and site-specific ablation in oxytocin system by making use of transgenic animals and virus vectors.  [Invited]
    Yoshida M, Takayanagi Y, Inutsuka A, Onaka T
    The 94th Annual Meeting of the Physiological Society of Japan  2017/03
  • 社会行動におけるオキシトシンの働き  [Invited]
    高柳友紀, 吉田匡秀, 尾仲達史
    第122回日本解剖学会総会・全国学術集会  2017/03
  • 視床下部特定回路の活動操作と活動記録  [Not invited]
    犬束歩, 吉田匡秀, 高柳友紀, 山中章弘, 尾仲達史
    第44回 自律神経生理研究会  2016/12
  • Do stroking stimuli induce a pleasat sensation in rats.  [Not invited]
    Okabe S, Takayanagi Y, Yoshida M, Inutsuka A, Onaka T
    日本動物心理学会第76回大会  2016/11
  • トランスジェニックラットを用いたペプチド選択性ニューロン破壊法の開発  [Not invited]
    渡辺純, 吉田匡秀, 高柳友紀, 尾仲達史
    第15回自治医科大学シンポジウム  2016/09
  • Neuroendocrine and behavioral responses to fear-related or affiliative stimuli: roles of oxytocin.  [Not invited]
    Onaka T, Takayanagi Y, Yoshida M, Okabe S
    The 93rd Annual Meeting of the Physiological Society of Japan  2016/03
  • 接触刺激に対するラット視床下部オキシトシン産生細胞の活性化と超音波発声  [Not invited]
    岡部祥太, 吉田匡秀, 高柳友紀, 尾仲達史
    第42回日本神経内分泌学会 第23回日本神経行動内分泌研究会 合同学術集会  2015/09
  • レジリエンスの分子機構  [Invited]
    吉田匡秀
    平成27年度栃木県小児保健会総会・研修会  2015/09
  • Noxious or Non-Noxious Inputs to Oxytocin Neurons: Possible Roles in the Control of Behaviors.  [Invited]
    Onaka T, Takayanagi Y, Yoshida M, Okabe S
    Parvo- and Magnocellular Symposium in Sendai  2015/09
  • Roles of the medial amygdala in the control of neuroendocrine responses to conditioned fear stimuli.  [Not invited]
    Onaka T, Yoshida M, Takayanagi Y
    The 92nd Annual Meeting of the Physiology Society of Japan  2015/03
  • Roles of oxytocin in the control of emotional and social behaviors.  [Not invited]
    Takayanagi Y, Yoshida M, Onaka T
    The 92nd Annual Meeting of the Physiology Society of Japan  2015/03
  • レジリエンスの分子機構:プロラクチン放出ホルモンの働き  [Not invited]
    吉田匡秀
    パブリックヘルス科学研究助成金 2013年度研究成果報告会  2014/12
  • Lesions of vasopressin neurons by use of vasopressin-DTR transgenic rats.  [Invited]
    Onaka T, Yoshida M, Takayanagi Y
    ICN 2014  2014/08
  • 下垂体後葉ホルモンとストレス・摂食・社会行動  [Invited]
    尾仲達史, 高柳友紀, 吉田匡秀
    創薬薬理フォーラム第21回シンポジウム  2013/09
  • Stress and energy metabolisms: roles of PrRP and oxytocin.  [Invited]
    Onaka T, Takayanagi Y, Yoshida M
    The 36th Naito Conference on“Molecular Aspects of Energy Balance and Feeding Behavior”  2013/09
  • The medial amygdala-medullary prolactin-releasing peptide neuron pathway mediates neuroendocrine responses to conditioned fear stimuli  [Not invited]
    Yoshida M, Takayanagi Y, Onaka T
    The 10th World Congress on Neuro- hypophysial Hormones (WCNH 2013)  2013/07
  • PrRP-オキシトシン系とリズム  [Not invited]
    尾仲達史, 高柳友紀, 山下雅子, 吉田匡秀
    文部科学省私立大学戦略的研究基盤形成支援事業シンポジウム2013  2013/06
  • Importance of the medial amygdala-medullary PrRP synthesizing neurons pathway in neuroendocrine responses to conditioned fear stimuli  [Not invited]
    Yoshida M, Takayanagi Y, Onaka T
    Neuro2013  2013/06
  • 摂食とストレスと社会記憶におけるオキシトシンの働き.  [Invited]
    尾仲達史, 高柳友紀, 吉田匡秀
    第117回日本解剖学会総会・全国学術集会  2012/03
  • Stress, energy metabolism and social behaviour: Roles of Neurohypophysial Hormones.  [Invited]
    Onaka, T, Takayanagi, Y, Yoshida, M
    The 9th World Congress on Neurohypophysial Hormones (WCNH 2011)  2011/07
  • ストレス、摂食、そして社会行動:オキシトシン、バゾプレシンの働き  [Invited]
    尾仲達史, 高柳友紀, 吉田匡秀
    第15回日本行動神経内分泌研究会、第15回鋤鼻研究会合同集会  2011/06
  • 雌雄マウスでの子育て行動誘導とオキシトシン受容体発現の調節  [Not invited]
    佐藤佳亮, 山下晃人, 吉田匡秀, 西森克彦
    第87回日本生理学大会,  2010
  • 分娩・母性行動に伴う視床下部視索上核OXT ニューロンでのOXTRの誘導的発現の解析.  [Not invited]
    林遼太郎, 山下晃人, 佐藤佳亮, 長田大知, 吉田匡秀, 西森克彦
    第86回日本神経科学大会,  2009
  • oxytocin受容体Venus-ノックインマ ウスを用いたoxytocin 受容体発現ニューロンの可視化  [Not invited]
    小野擁子, 吉田匡秀, 高柳友紀, 尾仲達史, 西森克彦
    2008年度日本農芸化学会大会,  2008
  • 社会行動樹立・制御における性差とオキシトシン受容体系.  [Not invited]
    西森克彦, 吉田匡秀, 高柳友紀, 尾仲達史, Larry Young
    第85回日本生理学会大会,  2008
  • 体温制御システムと社会行動制御に働くoxytocin/ oxytocin 受容体系.  [Not invited]
    西森克彦, 笠原好之, 吉田匡秀, 高柳友紀, 井樋慶一, 吉川和明, 尾仲達史
    第85回日本生理学会大会,  2008
  • Oxytocin receptor-Venus knock in mice enable direct visualization of oxytocin receptor expressing neurons.  [Not invited]
    Yoshida, M, Takayanagi, Y, Onaka, T, Nishimori, K
    WCNH2007  2007
  • オキシトシン受容体一Venus knock-in マウスによるオキシトシン受容体発現ニューロンの可視化  [Not invited]
    吉田匡秀, 高柳友紀, 尾仲達史, 西森克彦
    Neuro2007  2007
  • 分娩におけるオキシトシンとプロスタグランジンの機能解析  [Not invited]
    市野梓, 吉田匡秀, 高柳友紀, 佐藤佳, 杉本幸彦, 木村正, 西森克彦
    日本農芸化学会2007年度大会  2007
  • 分娩におけるオキシトシンとプロスタグランジンの機能解析.  [Not invited]
    吉田匡秀, 高柳友紀, 佐藤佳, 杉本幸彦, 木村正, 西森克彦
    第79回日本内分泌学会学術総会,  2006
  • オキシトシン受容体遺伝子欠損マウスは攻撃性が上昇する.  [Not invited]
    吉田匡秀, 高柳友紀, 尾仲達史, Larry Young, 西森克彦
    日本農芸化学会2005年度大会  2005
  • Roles of oxytocin receptor in reproductive functions and aggressive behavior of male mice.  [Not invited]
    Yoshida, M, Takayanagi, Y, Bielsky, I, Onaka, T, Young, L, Nishimori, K
    WCNH2005  2005
  • オキシトシン受容体による母性行動制御  [Not invited]
    高柳友紀, 吉田匡秀, 尾仲達史, Larry Young, 西森克彦
    日本農芸化学大会2005年度大会,  2005
  • Roles of oxytocin receptor in reproductive and nurturing function of mice  [Not invited]
    Takayanagi, Y, Kawamata, M, Bielsky, I, Yoshida, M, Kimura, T, Young. L, Nishimori, K
    WCNH2005  2005
  • サプトラクション法を用いた生殖制御関連遺伝子の探索  [Not invited]
    澤田欣也, 市野梓, 吉田匡秀, 山本融, 西森克彦
    第28回日本分子生物学会,  2005
  • オキシトシン受容体遺伝子欠損マウスは攻撃性が上昇する  [Not invited]
    吉田匡秀, 高柳友紀, 尾仲達史, Isadora Bielsky, Larry Young, 西森克彦
    第27回日本分子生物学会年会  2004
  • オキシトシン受容体遺伝子欠損マウスは攻撃性が上昇する  [Not invited]
    吉田匡秀, 高柳友紀, Isadora Bielsky, Larry Young, 西森克彦
    第26回日本分子生物学会年会,  2003
  • オキシトシン・オキシトシン受容体とプロスタグランジンF2a受容体の生殖における機能相関解析  [Not invited]
    高柳友紀, 吉田匡秀, 木村正, 西森克彦
    第76回日本内分泌学会学術総会,  2003
  • オキシトシン,オキシトシ ン受容体,プロスタグランジンF2a 受容体各遺伝子欠損マウスを用いた分娩システムの解明  [Not invited]
    高柳友紀, 武田一彦, 川又理樹, 吉田匡秀, 杉本幸彦, 西森克彦
    第25回日本分子生物学会年会,  2002

MISC

Research Grants & Projects

  • レジリエンスの神経回路基盤:プロラクチン放出ペプチド神経回路の役割
    文部科学省:科学研究費補助金(基盤研究(C))
    Date (from‐to) : 2017/04 -2020/03 
    Author : 吉田匡秀
  • 過剰摂取したリンを排出する中枢機構:老化の減速に果たす役割
    公益財団法人:浦上食品・食文化振興財団:浦上食品・食文化振興財団研究助成
    Date (from‐to) : 2020/03 
    Author : 吉田匡秀
  • 対人関係ストレスによる抑うつ作用の神経基盤 — 新規オキシトシン神経回路の機能解明
    公益財団法人小林国際奨学財団:小林国際奨学財団研究助成金
    Date (from‐to) : 2018 -2019 
    Author : 吉田匡秀
  • 共感性の神経内分泌制御
    文部科学省:新学術領域研究
    Date (from‐to) : 2013 -2018 
    Author : 尾仲達史
  • 文部科学省:科学研究費補助金(基盤研究(C))
    Date (from‐to) : 2014/04 -2017/03 
    Author : 吉田 匡秀
  • 文部科学省:科学研究費補助金(若手研究(B))
    Date (from‐to) : 2012/04 -2014/03 
    Author : 吉田 匡秀
  • ニューロンの樹状突起からの神経ペプチド放出の生理的役割
    自治医科大学:自治医科大学医学部研究奨励金
    Date (from‐to) : 2013 -2014 
    Author : 吉田匡秀
  • レジリエンスの分子機構:プロラクチン放出ホルモンの働き
    公益財団パブリックヘルスリサーチセンター:パブリックヘルス科学研究助成金
    Date (from‐to) : 2013 -2014 
    Author : 吉田匡秀
  • 文部科学省:科学研究費補助金(若手研究(B))
    Date (from‐to) : 2010/04 -2011/03 
    Author : 吉田 匡秀
     
    体液のナトリウムイオン(Na^+)濃度の恒常性は生命維持に必須である。これまでの我々の一連の研究から、Naチャンネル分子Na_xが脳内体液Na^+レベルセンサーとして機能し、塩分摂取を行動レベルで制御していることが明らかとなってきた。本研究は、脳弓下器官のエンドセリンB受容体によるNa_xの開口調節が動物個体の塩分摂取行動を制御する可能性を、分子・細胞から行動レベルに至る実験手法を駆使して統合的に明らかにすることを目指している。22年度は主に分子・細胞に着目した研究を行った。現在までの我々の研究から、Na_xは細胞外Na^+濃度の上昇により活性化されることが明らかとなっている。本研究により、Na_xはエンドセリンB受容体の活性化を介しても活性化が起こることを明らかとなった。一方でエンドセリンA受容体やアンジオテンシンII受容体を刺激してもNa_xの活性化は認められなかった。またエンドセリンB受容体の拮抗薬を用いた実験から細胞外Na^+濃度の上昇によるNa_xの活性化はエンドセリンによる開口と独立していることが明らかとなり、Na_xには2つの活性化メカニズムがあることが分かった。またエンドセリンB受容体の活性化によるNa_xの活性化はエンドセリンB受容体→プロテインキナーゼC→MAPK/ERKキナーゼ→ERK1/2経路の活性化を介していた。そこでNa_x自身がリン酸化修飾により開口している可能性を考え、Na_xに存在する細胞内領域がERKによりリン酸化を受けるかを確認した。その結果、Na_xに存在する5つの細胞内領域のうち、2つでERKによるリン酸化が認められた。電位依存性Na^+チャンネルファミリー分子が、少数ながらその細胞内領域のリン酸化を受けることにより活性化・不活性化の時間特性や電流量などが変化することは知られている。しかし、リン酸化によりチャンネルの開口が起こる現象に関しては全く報告がない。Na_xのリン酸化による開口が実証されれば、チャンネル分子の全く新しい開口機構が明らかとなると期待される。
  • 社会行動確立にオキシトシン/オキシトシン受容体システムが果たす役割の解析
    日本学術振興会:特別研究員(DC1)
    Date (from‐to) : 2005/04 -2008/03 
    Author : 吉田匡秀

Committee Membership

  • 2018 -2019   FAOPS   Program committee in 2019 convention


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