KINDAI UNIVERSITY


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KAGAWA Nao

Profile

FacultyDepartment of Life Science / Graduate School of Science and Engineering Research
PositionAssociate Professor
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/899-kagawa-nao.html
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Last Updated :2020/07/08

Education and Career

Education

  •  - 2001 , Hokkaido University
  •  - 1996 , Hokkaido University, School of Fisheries Sciences

Academic & Professional Experience

  •   2008 09 ,  - 2009 08 , Visiting scholar, Stanford University

Research Activities

Research Areas

  • Life sciences, Marine/Aquatic life sciences

Research Interests

  • fish behaviour and neuroendocrinology

Published Papers

  • Neurodevelopmental toxicity in the mouse neocortex following prenatal exposure to acetamiprid, Kagawa, N, T. Nagao, Journal of Applied Toxicology, Journal of Applied Toxicology, DOI: 10.1002/jat.3692, Jun. 2018 , Refereed
  • Mechanisms underlying neuro-in ammation and neurodevelopmental toxicity in the mouse neocortex following prenatal exposure to ethanol, Komada, M, N. Hara, S. Kawachi, K. Kawachi, N. Kagawa, T. Nagao, Y. Ikeda, Scientific Reports, Scientific Reports, DOI:10.1038/s41598-017-04289-1, Jul. 2017 , Refereed
  • Motor activities of newborns prenatally exposed to low-dose bisphenol A in diverse mouse strains, Kagawa,N, M. Komada, T. Nagao, Fundam. Toxicol. Sci., Fundam. Toxicol. Sci., 2, 79 - 82, May 2015 , Refereed
  • Potential roles of arginine-vasotocin in the regulation of aggressive behavior in the mudskipper (Periophthalmus modestus), Kagawa N, Y. Nishiyama, K. Kato, H. Takahashi, Y. Kobayashi, H. Sakamoto, T. Sakamoto, General and Comparative Endocrinology, General and Comparative Endocrinology, 194, 257 - 263, Sep. 2013 , Refereed
  • Social rank-dependent expression of arginine vasotocin in distinct preoptic regions in male Oryzias latipes., KAGAWA Nao, Journal of fish biology, Journal of fish biology, 82(1), 354 - 363, Jan. 2013 , Refereed
  • Social rank-dependent expression of gonadotropin-releasing hormones and kisspeptin in the medaka brain, Nao Kagawa, Sayuri Hirose, Keiko Fujimoto, Chihomi Nomura, Yuuma Fujita, Akira Honda, Mai Komori, GENERAL AND COMPARATIVE ENDOCRINOLOGY, GENERAL AND COMPARATIVE ENDOCRINOLOGY, 249, 48 - 54, Aug. 2017 , Refereed
    Summary:Social interactions regulate the expression of several neuropeptides that have a central role in the reproductive system of mammals. Nonmammalian vertebrates also have these neuropeptides or paralogs, however, studies on the social regulation of reproductive physiology in nonmammalian species are limited. In this study, we examined whether the expression of gonadotropin-releasing hormones (GnRHs) and kisspeptin (Kiss1) is affected by social hierarchy resulting from the outcomes of male-male competition in medaka fish (Oryzias latipes). Four males were introduced to each other in an experimental tank, and classified as the most aggressive dominant or the most submissive subordinate fish, based on the frequency of their aggressive acts during a short-term competition. Dominant and subordinate males maintained their social rank during a long-term competition. Immediately after short-term competition, gonadotropin-releasing hormone-3 (GnRH3) level in the olfactory bulb was significantly higher in subordinate males than in dominant males. After long-term competition, dominant males had high level of gonadotropin-releasing hormone-1 (GnRH1) in the preoptic area, whereas subordinate males had lower Kissl level in the nucleus ventral tuberis. On the other hand, the levels of gonadotropin-releasing hormone-2 (GnRH2) in the nucleus lateralis valvulae and Kissl in the nucleus posterioris periventricularis, and plasma 11-ketotestosterone (11-KT) concentration did not differ between subordinate and dominant males after the short- and long-term competitions. These results suggest that social hierarchy regulates the expression of GnRH1, GnRH3, and Kissl without affecting 11-KT level in male medaka. (C) 2017 Elsevier Inc. All rights reserved.
  • Arginine vasotocin neuronal development and its projection in the adult brain of the medaka, Nao Kagawa, Akira Honda, Akiko Zenno, Ryosuke Omoto, Saya Imanaka, Yusuke Takehana, Kiyoshi Naruse, NEUROSCIENCE LETTERS, NEUROSCIENCE LETTERS, 613, 47 - 53, Feb. 2016 , Refereed
    Summary:The neurohypophysial peptide arginine vasotocin (AVT) and its mammalian ortholog arginine vasopressin function in a wide range of physiological and behavioral events. Here, we generated a new line of trans genic medaka (Oryzias latipes), which allowed us to monitor AVT neurons by enhanced green fluorescent protein (EGFP) and demonstrate AVT neuronal development in the embryo and the projection of AVT neurons in the adult brain of avt-egfp transgenic medaka. The onset of AVT expression manifested at 2 days postfertilization (dpf) as a pair of signals in the telencephalon of the brain. The telencephalic AVT neurons migrated and converged on the preoptic area (POA) by 4 dpf. At the same stage, another onset of AVT expression manifested in the central optic tectum (OT), and they migrated to the ventral part of the hypothalamus (VH) by 6 dpf. In the adult brain, the AVT somata with EGFP signals existed in the gigantocellular POA (gPOA), magnocellular POA (mPOA), and parvocellular POA (pPOA) and in the VH. Whereas the major projection of AVT fibers was found from the pPOA and VH to the posterior pituitary, it was also found that AVT neurons in the three POAs send their fibers into wide regions of the brain such as the telencephalon, mesencephalon and diencephalon. This study suggests that the avt-egfp transgenic medaka is a useful model to explore AVT neuronal development and function. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Neurohypophysial Hormones Regulate Amphibious Behaviour in the Mudskipper Goby, Tatsuya Sakamoto, Yudai Nishiyama, Aoi Ikeda, Hideya Takahashi, Susumu Hyodo, Nao Kagawa, Hirotaka Sakamoto, PLOS ONE, PLOS ONE, 10(7), e0134605, Jul. 2015 , Refereed
    Summary:The neurohypophysial hormones, arginine vasotocin and isotocin, regulate both hydromineral balance and social behaviors in fish. In the amphibious mudskipper, Periophthalmus modestus, we previously found arginine-vasotocin-specific regulation of aggressive behavior, including migration of the submissive subordinate into water. This migration also implies the need for adaptation to dehydration. Here, we examined the effects of arginine vasotocin and isotocin administration on the amphibious behavior of individual mudskippers in vivo. The mudskippers remained in the water for an increased period of time after 1-8 h of intracerebroventricular (ICV) injection with 500 pg/g arginine vasotocin or isotocin. The 'frequency of migration' was decreased after ICV injection of arginine vasotocin or isotocin, reflecting a tendency to remain in the water. ICV injections of isotocin receptor antagonist with arginine vasotocin or isotocin inhibited all of these hormonal effects. In animals kept out of water, mRNA expression of brain arginine vasotocin and isotocin precursors increased 3- and 1.5-fold, respectively. Given the relatively wide distribution of arginine vasotocin fibres throughout the mudskipper brain, induction of arginine vasotocin and isotocin under terrestrial conditions may be involved also in the preference for an aquatic habitat as ligands for brain isotocin receptors.
  • Comparative analyses of lysophosphatidic acid receptor-mediated signaling, Nobuyuki Fukushima, Shoichi Ishii, Toshifumi Tsujiuchi, Nao Kagawa, Kazutaka Katoh, CELLULAR AND MOLECULAR LIFE SCIENCES, CELLULAR AND MOLECULAR LIFE SCIENCES, 72(12), 2377 - 2394, Jun. 2015 , Refereed
    Summary:Lysophosphatidic acid (LPA) is a bioactive lipid mediator that activates G protein-coupled LPA receptors to exert fundamental cellular functions. Six LPA receptor genes have been identified in vertebrates and are classified into two subfamilies, the endothelial differentiation genes (edg) and the non-edg family. Studies using genetically engineered mice, frogs, and zebrafish have demonstrated that LPA receptor-mediated signaling has biological, developmental, and pathophysiological functions. Computational analyses have also identified several amino acids (aa) critical for LPA recognition by human LPA receptors. This review focuses on the evolutionary aspects of LPA receptor-mediated signaling by comparing the aa sequences of vertebrate LPA receptors and LPA-producing enzymes; it also summarizes the LPA receptor-dependent effects commonly observed in mouse, frog, and fish.
  • Frequency and size of micronuclei induced in gill cells of medaka fish (Oryzias latipes) after whole-body exposure to clastogenic chemicals, Akinori Takai, Nao Kagawa, Masahiro Nakagawa, Yumi Watabe, Kazuo Fujikawa, DRUG AND CHEMICAL TOXICOLOGY, DRUG AND CHEMICAL TOXICOLOGY, 38(1), 67 - 72, Jan. 2015 , Refereed
    Summary:Medaka fish (Oryzias latipes) were whole-bodily treated with various doses of mitomycin C (MMC), ethylmethanesulfonate (EMS), cyclophosphamide (CP), diethylnitrosamine (DEN), or colchicine (COL) for 24 h, and the frequency of micronucleated cells (MNCs) was measured in the gills at 24 and 48 h after treatment. In the present experiments, MMC, CP, and DEN were recorded as efficient inducers of micronuclei at both sampling times, and none of the MNC frequencies recorded with these agents at 24 h significantly exceeded the corresponding frequency at 48 h. For EMS and COL, positive responses were recorded only 48 h after treatment. By comparison with the time-course data reported for radiation-induced MNCs in the same MN assay system, the clear responses observed at the 48-h time point for all the chemicals used were regarded as evidence of their delayed effects on micronucleus (MN) formation. The mean sizes of micronuclei induced after exposure to COL was significantly larger by a factor 2 as compared with that induced by X-irradiation, whereas those determined for the other four chemicals were almost equal to that induced by X-irradiation. These results demonstrate that the medaka gill-cell MN assay can detect chemically-induced chromosome damage, either directly or after metabolic activation, and spindle malfunction, and provide a basis for further development of the present assay system for testing cytogenetic activities of chemical agents.
  • Functional lysophosphatidic acid receptors expressed in Oryzias latipes, Yuji Morimoto, Shoichi Ishii, Jun-ichi Ishibashi, Kazutaka Katoh, Toshifumi Tsujiuchi, Nao Kagawa, Nobuyuki Fukushima, GENE, GENE, 551(2), 189 - 200, Nov. 2014 , Refereed
    Summary:Lysophosphatidic acid (LPA) signaling is known to play biological and pathophysiological roles in many types of animals. Medaka (Oryzias latipes) is an experimental fish that can be easily maintained, propagated, and analyzed, and whose genome has been completely sequenced. However, there is limited information available regarding medaka LPA receptors. Here, using information from the medaka genome database, we examine the genomic structures, expression, and functions of six LPA receptor genes, Lpar1-Lpar6. Our analyses reveal that the genomic structures of Lpar1 and Lpar4 are different from those deduced from the database. Functional analyses using a heterologous expression system demonstrate that all medaka LPA receptors except for LPA(5b) respond to LPA treatment with cytoskeletal changes. These findings provide useful information on the structure and function of medaka LPA receptor genes, and identify medaka as a useful experimental model for exploration of the biological significance of LPA signaling. (C) 2014 Elsevier B.V. All rights reserved.
  • Newborn mice exposed prenatally to bisphenol A show hyperactivity and defective neocortical development, Munekazu Komada, Saki Itoh, Kota Kawachi, Nao Kagawa, Yayoi Ikeda, Tetsuji Nagao, TOXICOLOGY, TOXICOLOGY, 323, 51 - 60, Sep. 2014 , Refereed
    Summary:The central nervous system is especially susceptible to toxic insults during development. Prenatal administration of bisphenol A (BPA) induces histologic anomalies in the dorsal telencephalon of the embryo. Whether these anomalies affect the morphogenesis and maturation of neuronal function of the newborn neocortex, however, is unknown. To evaluate the neurodevelopmental and behavioral effects of prenatal BPA exposure at 20 and 200 mu g/kg/day in newborn mice, we performed a detailed histologic analysis of the neocortex and tested for the presence of behavioral abnormalities in newborn mice prenatally exposed to BPA using our newly developed behavioral test. Observations of newborn mice prenatally exposed to BPA revealed abnormal neuronal distribution and layer formation, hypoplasia of layer 6b, and abnormal dopaminergic neuronal projections in the neocortex. Further, the newborn mice exhibited hyperactivity. These findings suggest that prenatal BPA exposure induces neurobehavioral toxicity associated with abnormal dopaminergic neuronal projections, and abnormal corticogenesis and lamination. Histologic and behavioral analyses of newborn mice are considered useful for assessing the neurodevelopmental and behavioral toxicity of chemicals. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
  • Early to middle gestational exposure to diethylstilbestrol impairs the development of labyrinth zone in mouse placenta, Nao Kagawa, Yoshiaki Saito, Tetsuji Nagao, CONGENITAL ANOMALIES, CONGENITAL ANOMALIES, 54(2), 116 - 119, May 2014 , Refereed
    Summary:This study was performed to clarify the involvement of impaired labyrinth zone (LZ) of the placenta in the developmental toxicity of diethylstilbestrol (DES). DES at 10g/kg per day was administered orally to mice on days 4 through 8 of gestation. Histological observation of the LZ and determination of blood glucose levels in dam and fetus were performed on day 13. A high frequency of embryonic death was observed in the DES group. DES induced the underdevelopment of the plexus vasculosus, extensive maternal blood space and the decreased expression of glucose transporters in the LZ, and a reduction of the glucose level in embryos. These findings suggest that impaired LZ development may be related to the embryolethality of DES.
  • Early to middle gestational exposure to diethylstilbestrol impairs the development of labyrinth zone in mouse placenta, Nao Kagawa, Yoshiaki Saito, Tetsuji Nagao, CONGENITAL ANOMALIES, CONGENITAL ANOMALIES, 54(2), 116 - 119, May 2014 , Refereed
    Summary:This study was performed to clarify the involvement of impaired labyrinth zone (LZ) of the placenta in the developmental toxicity of diethylstilbestrol (DES). DES at 10g/kg per day was administered orally to mice on days 4 through 8 of gestation. Histological observation of the LZ and determination of blood glucose levels in dam and fetus were performed on day 13. A high frequency of embryonic death was observed in the DES group. DES induced the underdevelopment of the plexus vasculosus, extensive maternal blood space and the decreased expression of glucose transporters in the LZ, and a reduction of the glucose level in embryos. These findings suggest that impaired LZ development may be related to the embryolethality of DES.
  • Neurobehavioral evaluation of mouse newborns exposed prenatally to low-dose bisphenol A, Tetsuji Nagao, Kota Kawachi, Nao Kagawa, Munekazu Komada, JOURNAL OF TOXICOLOGICAL SCIENCES, JOURNAL OF TOXICOLOGICAL SCIENCES, 39(2), 231 - 235, Apr. 2014 , Refereed
    Summary:There have been few neurobehavioral toxicology studies on newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants, by means of determining the newborn's motor activity applying the tare function of an analytical balance. Motor activities including crawling, pivoting, righting or tremors of mouse newborns were evaluated. Tremors of newborns of dams exposed to bisphenol A at 2, 20 or 200 mu g/kg/day on days 5 through 18 of gestation were significantly increased when evaluated on postnatal day 1, as well as those of newborns exposed prenatally to diethylstilbestrol at 0.5 mu g/kg/day. We suggest that our developed testing method may provide a useful addition to neurobehavioral assessment in very young rodents exposed to environmental hormone mimics.
  • Comparison of Aggressive Behaviors Between Two Wild Populations of Japanese Medaka, Oryzias latipes and O-sakaizumii, Nao Kagawa, ZOOLOGICAL SCIENCE, ZOOLOGICAL SCIENCE, 31(3), 116 - 121, Mar. 2014 , Refereed
    Summary:This study compared aggressiveness between two distinct wild populations of Japanese medaka: a Northern population, Oryzias sakaizumii, and a Southern population, O. latipes. When four males competed in intra-population contests, the social hierarchy was determined based on aggressive acts in both populations. Dominants of the Southern population showed higher aggressive acts than did dominants of the Northern population. Increased aggressiveness of Southern males compared with Northern males was also observed when a pair of Northern and Southern males were compared in inter-population contests. High expression of arginine vasotocin (AVT) in distinct preoptic regions were found in dominants and subordinates of the Southern population, but not in those of the Northern population. In contrast, neither 11-ketotestosterone nor cortisol levels in plasma differed between dominants and subordinates of either population, nor between pairs of the Northern and the Southern males. Taken together, these findings indicate that the two wild populations of medaka represent intriguing models for the study of neuroendocrinological correlates in behavioral traits underlying congeners of medaka fish.
  • Newly developed mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants, Tetsuji Nagao, Nao Kagawa, Munekazu Komada, JOURNAL OF APPLIED TOXICOLOGY, JOURNAL OF APPLIED TOXICOLOGY, 33(12), 1514 - 1519, Dec. 2013 , Refereed
    Summary:Although there have been a vast number of behavioral toxicology studies carried out on adult mice and rats, there have been few neurobehavioral studies utilizing their newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of chemicals, by means of determining the newborn's activity using the tare function of an analytical balance. The unstable weighing values resulting from movement of the newborn on the balance recorded by a personal computer every 0.1s, and the total activities of a newborn from the start time of weighing to individual times of evaluation were calculated. In addition, we confirmed the usefulness of our method by determining the activity of mouse newborns with microcephaly induced by prenatal exposure to a neurotoxicant, methylnitrosourea. Copyright (c) 2012 John Wiley & Sons, Ltd.
  • Developmental effects of oral exposure to diethylstilbestrol on mouse placenta, Tetsuji Nagao, Nao Kagawa, Yoshiaki Saito, Munekazu Komada, JOURNAL OF APPLIED TOXICOLOGY, JOURNAL OF APPLIED TOXICOLOGY, 33(11), 1213 - 1221, Nov. 2013 , Refereed
    Summary:Placental growth and function are of biological significance in that placental tissue promotes prenatal life and the maintenance of pregnancy. Exposure to synthetic estrogens causes embryonic mortality and placental growth restriction in mice. The aim of the present study was to examine the effects of diethylstilbestrol (DES) on placenta in mice. DES at 1, 5, 10 or 15 mu g kg(-1) day(-1), or 17-estradiol (E-2) at 50 mu g kg(-1) day(-1), was administered orally to ICR mice on days 4 through to 8 of gestation. Expression of ER, ER, ERR or ERR mRNA in the junctional or labyrinth zone of the placentas on day 13 was assessed using RT-PCR, as well as the embrynic mortality, embryonic and placental weight, histological changes of labyrinth and ultrastructural changes of the trophoblast giant cells (TGCs). Embryo mortalities in the DES 10 and 15 mu g kg(-1) day(-1) groups were markedly increased. No significant changes in embryonic and placental weight were observed in any DES- or E-2-exposed groups. Expression of ER mRNA in the junctional zone with male embryos in the 5 mu g kg(-1) day(-1) group was significantly higher than that in the control, whereas expression was not determined in the 15 mu g kg(-1) day(-1) group. Histological observation revealed that the placentas exposed to DES at 10 mu g kg(-1) day(-1) lacked the developing labyrinth. Ultrastructural observation of the TGCs showed poor rough-surfaced endoplasmic reticulum in the DES 10 mu g kg(-1) day(-1) group. The present data suggest that developmental changes induced by DES may be related to interference with the nutrition and oxygen exchange between mother and embryo or decreased protein synthesis, resulting in a high frequency of embryo mortality. Copyright (c) 2012 John Wiley & Sons, Ltd.

Works

  • Stress physiology in fish

Research Grants & Projects

  • ASSOCIATION OF AGGRESSIVE BEHAVIOR OF MEDAKA WITH EXPRESSION OF NEUROPEPTIDE