![](https://www.kindai.ac.jp/data/images/professor/899.jpg)
加川 尚(カガワ ナオ)
理工学部 生命科学科 | 教授/学科長 |
Last Updated :2024/08/31
■教員コメント
コメント
攻撃、生殖、摂食などの本能行動が脳のなかでどのように制御されているのか魚類を用いて調べています。特に、脳で発現する神経ペプチドに着目して研究しています。
■研究者基本情報
J-Global ID
研究キーワード
- 神経内分泌 行動生理 魚類 fish behaviour and neuroendocrinology
現在の研究分野(キーワード)
攻撃、生殖、摂食などの本能行動が脳のなかでどのように制御されているのか魚類を用いて調べています。特に、脳で発現する神経ペプチドに着目して研究しています。
■経歴
■研究活動情報
論文
- Hanae Tanaami; Saki Yamamoto; Suzuna Hayashi; Sumika Kawamoto; Hiroki Makino; Nao KagawaGeneral and Comparative Endocrinology 114355 - 114355 2023年08月 [査読有り]
- Effects of single and repeated heat stress on anxiety‐like behavior and locomotor activity in medaka fishAiri Otsuka; Yuki Shimomura; Honoka Sakikubo; Kensuke Miura; Nao KagawaFisheries Science 2021年10月 [査読有り]
- Takeru Tamaki; Nao Kagawa; Nobuyuki FukushimaBiochemical and biophysical research communications 568 1 - 7 2021年09月 [査読有り]
Lysophosphatidic acid (LPA) signaling plays diverse roles in the development of various vertebrates such as mammals and fish. The lamprey is a fish that retains ancestral features of vertebrates, but information regarding lamprey LPA receptor genes is limited. Here, using information from the lamprey genome database, we cloned two LPA receptor genes, Lpar1 and Lpar5, from the Japanese lamprey (Lethenteron camtschaticum). Lamprey Lpar1 had a high amino acid identity to mouse and medaka fish Lpar1, whereas Lpar5 amino acid sequences were more diverse between species. Our functional analyses using a heterologous expression system demonstrated that Lpar1 and Lpar5 responded to LPA treatment with G12/13-associated cellular responses, which are indicative of cytoskeletal actions. The existence of functional LPA receptors in the Japanese lamprey suggests that LPA receptor-dependent signals contribute to lamprey growth and development. - Immediate Early Gene Expression in Brain Regions Associated with the Social Behavioral Network After Male Competition in Medaka FishAiri Otsuka; Chihomi Nomura; Kensuke Miura; Akira Honda; Nao KagawaZOOLOGICAL SCIENCE 37 5 1 - 8 2020年09月 [査読有り]
- Munekazu Komada; Tetsuji Nagao; Nao KagawaJournal of applied toxicology : JAT 2020年07月 [査読有り]
Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate for the production of flexible polyvinyl chloride. Recent studies in humans reported a widespread DEHP exposure, raising concerns in infants whose metabolic and excretory systems are immature. DEHP is a potential endocrine-disrupting chemical, but the effects of postnatal DEHP exposure on neuronal development are unclear. The dentate gyrus (DG) is critical in the consolidation of information from short- to long-term memory, as well as spatial learning. We evaluated neurodevelopmental toxicity due to neonatal DEHP exposure by assessing neurogenesis in the DG. Newborn mice were orally administered DEHP from postnatal day (PND) 12 to 25. We performed immunostaining using neuronal markers at different stages to assess whether DEHP exposure affects neurons at specific differentiation stages at PND 26 and PND 110. We found that in mice, postnatal DEHP exposure led to a decrease in the number of Type-1, -2a, -2b, and -3 neural progenitor cells, as well as granule cells in the hippocampal DG at PND 26. Further, the results showed that neural progenitor cell proliferation and differentiation were also reduced in the hippocampal DG of the DEHP-exposed mice. However, no effect on memory and learning was observed. Overall, our results suggest that neurodevelopmental toxicity due to postnatal DEHP exposure might affect postnatal DG morphogenesis. - Physiological changes in response to social isolation in male medaka fishAiri Otsuka; Moeko Inahata; Yuki Shimomura; Nao KagawaFisheries Science 2020年06月 [査読有り]
- Airi Otsuka; Kenta Shimomura; Haruka Niwa; Nao KagawaJournal of fish biology 96 4 1014 - 1023 2020年04月 [査読有り]
Boldness and risk-taking behaviours in animals are important traits to obtain advantages such as habitation, food resources, reproductive success and social dominance. Risk-taking behaviour is influenced by physiological and environmental conditions; however, whether individual fish become bolder by the presence of conspecifics remains unknown. In this study, a light-dark preference test was conducted using medaka fish (Oryzias latipes) with or without a neighbouring conspecific. It was found that individual medaka male fish preferred a light environment and avoided a dark environment, whereas the display of a neighbouring conspecific enhanced the time the male spent in the dark environment (i.e., this condition encouraged risk-taking). The blood glucose level increased in fish confined to the dark condition but did not increase in light-preferring fish and risk-taking fish. Large somata expressing tyrosine hydroxylase, which is the rate-limiting enzyme in dopamine synthesis, were detected in the telencephalic and diencephalic brain regions in risk-taking medaka, whereas large somata were detected in the diencephalic region in medaka confined to the dark condition. These findings indicated that medaka is a good fish model to explore the central roles of dopaminergic neurons in the telencephalon and the diencephalon, which regulate risk-taking behaviour. - Nao Kagawa; Tetsuji NagaoCongenital anomalies 2020年03月 [査読有り]
Bisphenol A (BPA) is known to cause abnormal neurogenesis in the developing neocortex. The mechanisms of BPA toxicity concerning neuroinflammatory-related endpoints are incompletely characterized. To evaluate the microglial morphology and the gene expression of pro-inflammatory cytokines in the newborn neocortex, ICR mice were exposed to BPA 200 μg/kg/d on gestational day 6 through post-partum day 21. Weanlings exposed during prenatal and postnatal period to BPA showed an increased number of amoeboid-type microglia, a microglial differentiation disruption (the M1/M2 microglial ratio), and an abnormal expression of genes encoding pro-inflammatory factors. These findings suggest that the well-known neurodevelopmental toxicity of BPA may be related to an increased microglial activation and neuroinflammation in the neocortex. - Munekazu Komada; Tetsuji Nagao; Nao KagawaThe Journal of toxicological sciences 45 10 639 - 650 2020年 [査読有り]
Bisphenol A (BPA), an endocrine disruptor with estrogenic effects, is widely used as a raw material for manufacturing polycarbonate plastic and epoxy resins. Prenatal and postnatal exposure to BPA affects brain morphogenesis. However, the effects of prenatal and postnatal BPA exposure on postnatal neurogenesis in mice are poorly understood. In this study, we developed a mouse model of prenatal and postnatal BPA exposure and analyzed its effects on hippocampal neurogenesis. The hippocampal dentate gyrus is vulnerable to chemical exposure, as neurogenesis continues in this region even after birth. Our results showed that in mice, prenatal and postnatal BPA exposure decreased the number of type-1, 2a, 2b, and 3 neural progenitor cells, as well as in granule cells, in the hippocampal dentate gyrus on postnatal days 16 and 70. The effect of prenatal and postnatal BPA exposure on neural progenitors were affected at all differentiation stages. In addition, prenatal and postnatal BPA exposure affects the maintenance of long-term memory on postnatal day 70. Our results suggest that neurodevelopmental toxicity due to prenatal and postnatal BPA exposure might affect postnatal morphogenesis and functional development of the hippocampal dentate gyrus. - Akira Nakayama; Manami Yoshida; Nao Kagawa; Tetsuji NagaoJournal of applied toxicology : JAT 39 6 877 - 887 2019年06月 [査読有り]
Acetamiprid (ACE) and imidacloprid (IMI) are widely used neonicotinoid pesticides. They bind selectively to insect nicotinic acetylcholine receptors (nAChRs) and are considered non-hazardous to mammals. Few studies have assessed the activation of vertebrate nAChRs and the neurodevelopmental toxicity following in utero or neonatal exposure to neonicotinoids; therefore, we evaluated the effects of ACE or IMI exposure on neurogenesis and microglial profiles in the developing hippocampal dentate gyrus (DG) of mouse neonates. Mice were exposed to ACE, IMI (both 5 mg/kg/day) or nicotine (0.5 mg/kg/day) from postnatal day (P)12 to P26 by oral gavage. On P27, brains were removed, and neurogenesis and microglial activation in the hippocampal DG were examined via immunohistochemistry. A reduction in neurogenesis in the hippocampal DG of neonates following ACE, IMI and nicotine treatment was found. Additionally, neonicotinoid-exposed newborns showed an increase in the number of amoeboid-type and activated M1-type microglia. These results suggest that exposure to ACE and IMI impairs neurogenesis and alters microglial profiles in the developing hippocampal DG following oral dosing in an early postnatal period. A better understanding of the potential effects of these pesticides on human infant health is an important goal of our research. - Yuki Shimomura; Moeko Inahata; Mai Komori; Nao KagawaZoological science 36 3 223 - 230 2019年06月 [査読有り]
Serotonin (i.e., 5-hydroxytryptamine [5-HT]) plays a key role in stress responses in vertebrates. In mammals and teleosts, tryptophan hydroxylase (Tph), a rate-limiting enzyme in the biosynthesis of 5-HT, includes two paralogs: Tph 1 and Tph 2. The response of the Tphs to stress has been reported in mammals, but less is known about the responses of these enzymes to stress in fish. In the present study, we examined whether heat stress affects the mRNA expression of these Tphs in the brain of medaka fish (Oryzias latipes). We also determined the concentration of 5-HT in the brain, the mRNA expression of heat shock protein 90 alpha (Hsp90α) in the liver, plasma cortisol concentration, and blood glucose concentration in medaka. Whole-body exposure to repeated heat stress significantly decreased the mRNA expression of Tph1 and Tph2 in male and female medaka, whereas single heat stress did not affect the expression of either of the mRNAs. The 5-HT concentration also decreased significantly after repeated heat stress sessions in both sexes, but did not decrease after a single heat stress session. After single and repeated heat stress sessions, Hsp90α mRNA expression increased in both sexes; however, increments in the concentrations of plasma cortisol and blood glucose occurred in male, but not in female, medaka. These results suggest that both types of Tphs are involved in reducing 5-HT in the brain and are reliable indicators of chronic stress response in both sexes. However, stress responses in plasma cortisol and blood glucose concentrations differ between male and female medaka. - Kagawa, N; T. NagaoJournal of Applied Toxicology DOI: 10.1002/jat.3692 2018年06月 [査読有り]
- Nao Kagawa; Sayuri Hirose; Keiko Fujimoto; Chihomi Nomura; Yuuma Fujita; Akira Honda; Mai KomoriGENERAL AND COMPARATIVE ENDOCRINOLOGY 249 48 - 54 2017年08月 [査読有り]
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. - Munekazu Komada; Nao Hara; Satoko Kawachi; Kota Kawachi; Nao Kagawa; Tetsuji Nagao; Yayoi IkedaSCIENTIFIC REPORTS 7 2017年07月 [査読有り]
Fetal alcohol spectrum disorders (FASD) constitute a wide range of disorders that arise from prenatal exposure to ethanol (EtOH). However, detailed reports regarding the adverse effects of prenatal EtOH exposure on neocortical morphology and its underlying pathogenic mechanisms are limited. In the present study, we aimed to characterize the anatomical abnormalities of neocortical development and their correlation with microglial properties and neuro-inflammation in a mouse model of FASD. We evaluated the development and maturation of the neocortex in ICR mice prenatally exposed to 25% (w/v) EtOH using histological and molecular analyses. Reduced proliferation and excessive cell death were observed in the dorsal telencephalon. Abnormal neuronal distribution, layer formation, and dopaminergic neuronal projections were observed in the neocortex. Disruption of microglial differentiation (M-1/M-2 microglial ratio) and abnormal expression of pro-inflammatory and neurotrophic factors were induced, and these abnormalities were ameliorated by co-treatment with an antiinflammatory drug (pioglitazone). FASD model mice displayed histological abnormalities, microglial abnormalities, and neuro-inflammation in both the embryonic and newborn stages. Thus, antiinflammatory therapeutics may provide a novel preventive approach for the treatment of FASD. - Munekazu Komada; Yuuya Gendai; Nao Kagawa; Tetsuji NagaoToxicology Letters 259 69 - 79 2016年09月 [査読有り]
Di(2-ethylhexyl) phthalate (DEHP) is currently the most commonly used phthalate for the production of flexible polyvinyl chloride. Phthalates including DEHP have been labeled as potential endocrine disruptors. The effect on the development of the neocortex, however, is unknown. To evaluate the neurodevelopmental effects of prenatal DEHP exposure at 1 and 100 mg/kg/day or 100 and 500 mg/kg/day in fetal and newborn mice, we performed a detailed histologic analysis of the developing dorsal telencephalon and neocortex. The observation of fetuses exposed to DEHP revealed reductions of proliferation and neurogenesis (1 and 100 mg/kg) and an increase in cell death (500 mg/kg). In addition, the newborns prenatally exposed to DEHP showed an abnormal neuronal distribution and a decrease in neurons. These findings suggest that prenatal DEHP exposure induces neurodevelopmental toxicity associated with the neural stem cell niche and corticogenesis. - Nao Kagawa; Akira Honda; Akiko Zenno; Ryosuke Omoto; Saya Imanaka; Yusuke Takehana; Kiyoshi NaruseNEUROSCIENCE LETTERS 613 47 - 53 2016年02月 [査読有り]
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. - Tatsuya Sakamoto; Yudai Nishiyama; Aoi Ikeda; Hideya Takahashi; Susumu Hyodo; Nao Kagawa; Hirotaka SakamotoPLOS ONE 10 7 e0134605 2015年07月 [査読有り]
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. - Nobuyuki Fukushima; Shoichi Ishii; Toshifumi Tsujiuchi; Nao Kagawa; Kazutaka KatohCELLULAR AND MOLECULAR LIFE SCIENCES 72 12 2377 - 2394 2015年06月 [査読有り]
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. - Kagawa,N; M. Komada; T. NagaoFundam. Toxicol. Sci. 2 2 79 - 82 一般社団法人 日本毒性学会 2015年05月 [査読有り]
Studies on the low-dose effects of xenoestrogens have yielded conflicting results that may have resulted from differences in estrogen sensitivity between the mouse strains used. We developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental chemicals, by means of determining a newborn's motor activity through applying the tare function of an analytical balance. Motor activities including crawling, pivoting, and tremors of C57BL/6J and ICR mouse newborns exposed to bisphenol A (BPA) at 200 µg/kg/day on embryonic days 6 through 18 were evaluated for 5 min on postnatal day 1 by the testing method. Motor activities of mature male offspring exposed prenatally to BPA were also evaluated in wheel cage and open field tests. Maternal BPA oral dosing increased the motor activity in newborns of both strains and mature offspring of the C57BL/6J strain. The findings indicate that both mouse strains provide adequate models for the newborn neurobehavioral study of prenatal exposure to environmentally relevant levels of estrogen-mimicking chemicals. - Akinori Takai; Nao Kagawa; Masahiro Nakagawa; Yumi Watabe; Kazuo FujikawaDRUG AND CHEMICAL TOXICOLOGY 38 1 67 - 72 2015年01月 [査読有り]
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. - ビスフェノールAの妊娠期及び授乳期投与はマウス歯状回におけるニューロン新生を低下させる前田 朋生; 加川 尚; 駒田 致和; 池田 やよい; 菅野 純; 長尾 哲二環境ホルモン学会研究発表会要旨集 17回 130 - 130 日本内分泌撹乱物質学会 2014年12月
- Yuji Morimoto; Shoichi Ishii; Jun-ichi Ishibashi; Kazutaka Katoh; Toshifumi Tsujiuchi; Nao Kagawa; Nobuyuki FukushimaGENE 551 2 189 - 200 2014年11月 [査読有り]
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. - Munekazu Komada; Saki Itoh; Kota Kawachi; Nao Kagawa; Yayoi Ikeda; Tetsuji NagaoTOXICOLOGY 323 51 - 60 2014年09月 [査読有り]
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. - Nao Kagawa; Yoshiaki Saito; Tetsuji NagaoCONGENITAL ANOMALIES 54 2 116 - 119 2014年05月 [査読有り]
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. - Nao Kagawa; Yoshiaki Saito; Tetsuji NagaoCONGENITAL ANOMALIES 54 2 116 - 119 2014年05月 [査読有り]
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. - Tetsuji Nagao; Kota Kawachi; Nao Kagawa; Munekazu KomadaJOURNAL OF TOXICOLOGICAL SCIENCES 39 2 231 - 235 2014年04月 [査読有り]
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. - Nao KagawaZOOLOGICAL SCIENCE 31 3 116 - 121 2014年03月 [査読有り]
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. - Tetsuji Nagao; Nao Kagawa; Munekazu KomadaJOURNAL OF APPLIED TOXICOLOGY 33 12 1514 - 1519 2013年12月 [査読有り]
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. - Nao Kagawa; Yudai Nishiyama; Kanoko Kato; Hideya Takahashi; Yasuhisa Kobayashi; Hirotaka Sakamoto; Tatsuya SakamotoGeneral and Comparative Endocrinology 194 257 - 263 2013年12月 [査読有り]
The hypothalamic hormones, arginine-vasotocin (VT) and isotocin (IT), play central roles in osmoregulation and in the regulation of social behaviors including aggressive behavior in many vertebrates including fish. Here, we examined whether these hormones are associated with aggressive behavior in the mudskipper (Periophthalmus modestus). The mudskipper is an amphibious fish, which lives in the brackish water of river mouths and displays unique aggressive behavior. Upon introduction to each other in an experimental tank with aquatic and terrestrial areas, a pair of males can be classified as aggressive dominant or submissive subordinate based on the frequency of their aggressive acts, which is significantly higher in dominant male. Additionally, the length of stay in terrestrial area of dominant was longer than that of the subordinate. The latter remained in aquatic area almost throughout the period of behavioral observation. The expression of brain VT mRNA was significantly higher in subordinate than in dominant, whereas neither IT mRNA expression nor plasma cortisol level differed between subordinate and dominant male. On the other hand, an intracerebroventricular injection of VT increased aggressive behaviors in mudskippers. In addition to known roles of VT in mediation of aggressive behavior, these results may shed light on the role of endogenous VT toward water migration in submissive mudskippers. The amphibious fish is a valuable experimental model to observe the relationship between effects of central VT on the osmoregulation and social behavioral regulation in vertebrates. © 2013. - Tetsuji Nagao; Nao Kagawa; Yoshiaki Saito; Munekazu KomadaJOURNAL OF APPLIED TOXICOLOGY 33 11 1213 - 1221 2013年11月 [査読有り]
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. - Nao KagawaJournal of Fish Biology 82 1 354 - 363 2013年01月 [査読有り]
This study examined arginine vasotocin (AVT) expression in the brains of dominant and subordinate male medaka Oryzias latipes after short- and long-term competition. High AVT expression in distinct preoptic regions was found in dominants and subordinates within minutes of encountering each other. During long-term competition, AVT expression remained high in dominants but not in subordinates. © 2012 The Author. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles. - Naohito Okudaira; Yoshihiko Uehara; Kazuo Fujikawa; Nao Kagawa; Akira Ootsuyama; Toshiyuki Norimura; Ken-ichi Saeki; Takehiko Nohmi; Ken-ichi Masumura; Tsuneya Matsumoto; Yoichi Oghiso; Kimio Tanaka; Kazuaki Ichinohe; Shingo Nakamura; Satoshi Tanaka; Tetsuya OnoRadiation research 173 2 138 - 47 2010年02月 [査読有り]
The effect of dose rate on radiation-induced mutations in two somatic tissues, the spleen and liver, was examined in transgenic gpt delta mice. These mice can be used for the detection of deletion-type mutations, and these are the major type of mutation induced by radiation. The dose rates examined were 920 mGy/min, 1 mGy/min and 12.5 microGy/min. In both tissues, the number of mutations increased with increasing dose at each of the three dose rates examined. The mutation induction rate was dependent on the dose rate. The mutation induction rate was higher in the spleen than in the liver at the medium dose rate but was similar in the two tissues at the high and low dose rates. The mutation induction rate in the liver did not show much change between the medium and low dose rates. Analysis of the molecular nature of the mutations indicated that 2- to 1,000-bp deletion mutations were specifically induced by radiation in both tissues after high- and low-dose-rate irradiation. The occurrence of deletion mutation without any sequence homology at the break point was elevated in spleen after high-dose-rate irradiation. The results indicate that the mutagenic effects of radiation in somatic tissues are dependent on dose rate and that there is some variability between tissues. - Tetsuya Ono; Yoshihiko Uehara; Naohito Okudaira; Kazuo Fujikawa; Nao Kagawa; Mitsuaki Yoshida; Isamu Hayata; Takehiko Nohmi; Tsuneya Matsumoto; Yoichi Oghiso; Kimio Tanaka; Kazuaki Ichinohe; Shingo Nakamura; Satoshi TanakaData Science Journal 8 BR36 - BR41 2009年09月 [査読有り]
To understand the effects of low dose-rate radiation on genome structure in vivo, we examined gene mutation and chromosomal abnormality in mouse tissues. The mutation was studied on transgenes in the spleen and liver and also on the Dlb1 gene in intestinal stem cells. The mice were irradiated for 483 consecutive days at three dose-rates of 0.0323, 0.65, and 12.5 μGy/min, which resulted in total doses of 21, 414, and 8,000 mGy, respectively. Statistically significant increases were observed for all indices examined when the total dose was 8,000 mGy, whereas no significant difference was observed with 21 mGy or 414 mGy. - Takai A; Kagawa N; Fujikawa KGenes and Environment 30 2 48 - 52 日本環境変異原学会 2008年 [査読有り]
The frequency of micronucleated cells (MNCs) was measured in acridine orange (AO) stained kidney cells obtained from male and female medaka fish (Oryzias latipes) of known body weight before and after X-irradiation at a dose of 4Gy. The MNC frequency in the kidney cells obtained from untreated and X-ray treated fish did not vary in correlation with the body weight in either gender, and neither did it show a significant gender-related difference. In both the untreated and treated groups, the number of MNCs in kidney cells per fish appeared to follow a Poisson distribution. These results are in agreement with those previously reported for the MNC frequency in gill cells of medaka fish. The average MNC frequency in kidney cells for the untreated fish was 0.4‰ (12/30000), which was significantly lower than 0.8‰ (24/30000) reported for gill cells. Similarly, a relatively lower frequency of X-ray-induced MNCs was evident for kidney cells (2.2‰; 69/30000) vs. gill cells (6.3‰; 191/30000). These results combined with previous reports support the use of AO to detect micronucleus formation in kidney cells, and further indicate that the kidney cell micronucleus assay can be used as a reliable and coincidently applied adjunct to the gill cell assay for medaka fish. - Nao Kagawa; Masahiko Shimura; Akinori Takai; Satoru Endo; Kazuo FujikawaMutation research 556 1-2 93 - 9 2004年11月 [査読有り]
Following whole-body irradiation of ICR mice with various doses of fission neutrons or X-rays, the frequency of micronuclei (MNs) in peripheral blood reticulocytes was measured at 12 h intervals beginning immediately after irradiation and ending at 72 h after irradiation. The resulting time-course curve of MN frequency had a clear peak 36 h after irradiation, irrespective of the type of radiation applied and the dose used. The MN frequency, averaged as the unweighted mean over the experimental time course, showed a linear increase with increasing dose of either fission neutrons or X-rays. The linear response to X-rays supports reported conclusion that induction of MN formation in reticulocytes is a dose-rate independent phenomenon. The relative biological effectiveness (RBE) of fission neutrons to X-rays for MN induction was estimated to be 1.9 +/- 0.3. This value is considerably lower than the RBE value of 4.6 +/- 0.5 reported for the same fission neutrons for induction of lymphocyte apoptosis in the thymus of ICR mice that represents dose-rate independent, one-track event. Based on these results, we propose that MNs increased in reticulocytes after irradiation mostly represent acentric fragments caused by single chromosome breaks, and that some confounding factor is operating in erythroblasts for the formation of aberrations from non-rejoining DNA double-strand breaks more severely after high-LET radiation than after low-LET radiation. - Nao KagawaZoological science 21 11 1085 - 9 2004年11月 [査読有り]
Geldanamycin (GA), a specific inhibitor of the chaperoning function of heat-shock protein 90 (Hsp90), has been shown to mimic heat shock (HS) in inducing expression of Hsp90, Hsp72 and other Hsps in unstressed mammalian cells. In the present study, intra-cerebral treatment of goldfish with GA (at a dose of 0.1 microg/g-body weight) diminished basal Hsp90 level to a 30-40% level in the brain, without affecting the basal Hsp72 level, as assayed 28-48 h after treatment. Whole-body exposure to HS significantly increased Hsp90 level in GA-untreated fish but not in GA-treated fish, while it significantly increased Hsp72 level in both GA-untreated and -treated fish. In both GA-untreated and -treated fish, plasma cortisol (PC) levels increased considerably 4 h after HS and then decreased in a time-dependent manner to the control levels 24 h after HS, showing no evidence of a GA effect on the time course of PC level. These results suggest that in the brain of goldfish, Hsp90 may not be involved as a key factor either in regulating Hsp72 expression both before and after HS or in the feedback regulation of HS-increased PC level, and support the idea that GA can be used in fish brain as a tool in elucidating the role of Hsp90 in complicated, Hsp-mediated biological processes. - Akinori Takai; Nao Kagawa; Kazuo FujikawaMutation Research - Genetic Toxicology and Environmental Mutagenesis 558 1-2 131 - 136 2004年03月 [査読有り]
The frequency of micronucleated cells (MNCs) was measured in acridine-orange (AO) stained RNA-rich gill cells from male and female medaka (Oryzias latipes) fish of known body weight. Spontaneous MNC frequencies were not significantly correlated with body weight, despite the fact that the heaviest of the 30 fish used outweighed the lightest by a factor of 3. Average MNC frequencies were identical in males and females at 0.8‰. An X-ray dose of 4Gy increased the frequency of MNCs over the spontaneous level in all 30 of the fish used, reaching a level of 7.2‰ on average when assayed 24h after exposure. In X-ray treated fish, MNC frequency and body weight were not significantly correlated, nor was there any difference between the sexes. These and other results support our primary conclusion that AO-staining is suitable for the medaka micronucleus assay in gill cells, and indicate that male and female medaka fish are similarly and size-independently susceptible to both spontaneous and X-ray induced micronucleus formation in gill cells. © 2003 Elsevier B.V. All rights reserved. - Akinori Takai; Nao Kagawa; Kazuo FujikawaMutation research 558 1-2 131 - 6 2004年03月 [査読有り]
The frequency of micronucleated cells (MNCs) was measured in acridine-orange (AO) stained RNA-rich gill cells from male and female medaka (Oryzias latipes) fish of known body weight. Spontaneous MNC frequencies were not significantly correlated with body weight, despite the fact that the heaviest of the 30 fish used outweighed the lightest by a factor of 3. Average MNC frequencies were identical in males and females at 0.8 per thousand. An X-ray dose of 4 Gy increased the frequency of MNCs over the spontaneous level in all 30 of the fish used, reaching a level of 7.2 per thousand on average when assayed 24 h after exposure. In X-ray treated fish, MNC frequency and body weight were not significantly correlated, nor was there any difference between the sexes. These and other results support our primary conclusion that AO-staining is suitable for the medaka micronucleus assay in gill cells, and indicate that male and female medaka fish are similarly and size-independently susceptible to both spontaneous and X-ray induced micronucleus formation in gill cells. - Akinori Takai; Nao Kagawa; Kazuo FujikawaEnvironmental and molecular mutagenesis 44 2 108 - 12 2004年 [査読有り]
Medaka fish (Oryzias latipes) were exposed to various doses of X-rays or fast neutrons, and the frequency of micronucleated cells (MNCs) was measured in gills sampled at 12- or 24-hr intervals from 12 to 96 hr after exposure. The resulting time course of MNC frequency was biphasic, with a clear peak 24 hr after exposure, irrespective of the kind of radiation applied and the dose used. The half-life of MNCs induced in the gill tissues by the two exposures fluctuated around 28 hr, with no significant dose-dependent trend for either X-ray- or neutron-exposed fish. As assayed 24 hr after exposure, the MNC frequency increased linearly over the control level with increasing doses of both X-rays and fast neutrons. The relative biological effectiveness (RBE) of fast neutrons to X-rays for MNC induction was estimated to be 4.3 +/- 0.6. This value is close to the RBE value of 5.1 +/- 0.3 reported for fast neutron induction of somatic crossing-over mutations in Drosophila melanogaster that arise from recombination repair of DNA double-strand breaks. These results and other data support our conclusion that the medaka gill cell micronucleus assay is a reliable short-term test for detecting potential inducers of DNA double-strand breaks. - Tetsuji Nagao; Nao Kagawa; Madoka Nakagomi; Kazuo FujikawaAdvances in experimental medicine and biology 518 211 - 7 2003年 [査読有り]
- Nao Kagawa; Yasuo MugiyaZoological science 19 7 735 - 40 2002年07月 [査読有り]
We previously found that when goldfish were exposed to a potential predator, bluegills, the goldfish experienced an increase in HSP70 mRNA expression in the brains and increased plasma cortisol levels. In the present study, we examined the potential causative relationship between HSP70 mRNA expression and plasma cortisol levels. Cortisol agonists (corticotropin releasing factor and cortisol) and antagonists (metyrapone and betamethasone) were used to modulate plasma cortisol levels. HSP70 mRNA expression and plasma cortisol levels were analyzed by Northern blotting and ELISA, respectively. Goldfish treated with the cortisol agonists showed marked increases in plasma cortisol levels and also in brain HSP70 mRNA expression. When goldfish were exposed to bluegills, plasma cortisol levels increased and HSP70 mRNA expression was enhanced after 6 hr. However, pre-treatment with the cortisol antagonists 24 hr prior to the exposure inhibited the enhancement as well as the increase in plasma cortisol levels. These results suggest that plasma cortisol plays a key role in the enhancement of brain HSP70 mRNA expression in goldfish stressed by exposure to bluegills. - Nao Kagawa; Yasuo MugiyaFisheries Science 68 1315 - 1316 2002年 [査読有り]
- Un-GiHwang; NaoKagawa; YasuoMugiyaGeneral and Comparative Endocrinology 119 1 69 - 76 2000年 [査読有り]
Effects of Al and Cd on vitellogenin (VTG) and VTG mRNA induction by estradiol-17 β (E2) were examined in primary hepatocyte cultures of rainbow trout. Hepatocytes were precultured for 2 days and then E2 (2 x 10-6 M) and Al (10-6-10-4 M) or Cd (10-9-10-6 M) were simultaneously added to the incubation medium. Hepatocytes were cultured for 5 more days. Media and hepatocytes were then analyzed by SDS-PAGE and Northern blotting for VTG and VTG mRNA, respectively. These metals had no appreciable effect on the viability of hepatocytes in culture. However, Al and Cd interfered with VTG production and VTG mRNA expression. Al reduced VTG production in a concentration-dependent way and a significant reduction occurred at Al concentrations greater than 5 x 10-5 M. VTG mRNA expression also decreased with a negative correlation with Al concentrations (r = -0.98). The inhibition of VTG production by Cd was not concentration-dependent. This metal markedly inhibited VTG production and VTG mRNA expression at 10-6 M. The Al-induced inhibition of VTG production was restored 7 days after Al removal, but the Cd-induced inhibition was not restored. These results suggest that Al and Cd inhibit VTG production at the transcriptional level to reduce VTG mRNA expression by different mechanisms. (C) 2000 Academic Press. - Nao Kagawa; Yasuo MugiyaZoological Science 17 8 1061 - 1066 2000年 [査読有り]
The effect of psychological stress on HSP70 mRNA in the brains and plasma cortisol levels in goldfish was examined. Stress was induced by exposure to a predator (bluegills). HSP70 mRNA and cortisol were determined by Northern blotting and ELISA, respectively. Goldfish exposed to four predators in the same tank without a partition showed marked increases in HSP70 mRNA and cortisol levels 6 hr and 12 hr after commencement of exposure. When goldfish were separated from bluegills with a net partition, HSP70 mRNA expression was enhanced after 6 hr, and returned to the control level after 12 hr. Plasma cortisol levels increased after 2 hr, and returned to the control level after 6 hr. When goldfish were placed in a transparent tank around which bluegills were swimming, HSP70 mRNA expression and cortisol levels increased after 6 hr and 12 hr. Goldfish exposed to water circulating through a tank with bluegills showed no sign of changes in HSP70 mRNA expression or cortisol levels. These results suggest that psychological stress enhanced HSP70 mRNA expression in the brains and increased plasma cortisol levels via visual perception. - N. Kagawa; K. Ryo; Y. MugiyaFish Physiology and Biochemistry 21 2 103 - 110 1999年 [査読有り]
Induction of stress protein (HSP70) was studied in goldfish (Carassius auratus) reared with bluegills (Lepomis macrochirus), a predator of small fish. HSP70 was identified by Western blotting and quantified by optical density after SDS-PAGE. The expression of HSP70 was significantly enhanced in the brains of goldfish reared with bluegills for 6 and 12 h in a single tank. The hepatopancreas and the kidney were not affected by the treatment. When goldfish were separated from bluegills with a partition net (1 × 1 cm mesh size), this protein also increased in the brains after 6 h but then returned to the control level after 12 h. When the goldfish and bluegills were kept in separate tanks and were not able to see each other but were connected by circulating water, HSP70 levels in the goldfish were unaffected. Immunohistochemical observations indicated that an anti-HSP70 antibody was found to react predominantly with the optic and vagal lobes of the brains. These results suggest that visual perception plays a primary role in enhancement of HSP70 expression in the goldfish reared with bluegills.
MISC
共同研究・競争的資金等の研究課題
- 日本学術振興会:科学研究費助成事業 基盤研究(C)研究期間 : 2021年04月 -2024年03月代表者 : 加川 尚本研究は、魚類の大胆または慎重行動が仲間の有無によってどのように調節されるか、また、それらの行動調節に神経ペプチドや神経伝達物質が関与するかを解明することを目的としている。本年度は、メダカを用いてrisk-taking行動試験を行い、同種他個体の存在下で大胆行動をとる個体と、単独で慎重行動をとる個体を得た後、両者の脳内アルギニンバソトシン(AVT)の発現量および各脳領域における神経活動活性を解析、比較した。 大胆行動をとった個体では、脳視床下部の視索前核に相当するgPOA領域におけるAVT発現量が慎重行動をとった個体に比べて高い傾向がみられた。一方、AVT神経の脳内投射領域は大胆行動をとる個体および慎重行動をとる個体のいずれにおいても、同様に観察され、大きな違いは認められなかった。これらの結果から、大胆個体と慎重個体では、AVT神経の機能する脳領域に相違はなく、特定の脳領域で受容されるAVT量が増えることで大胆行動が亢進される可能性が示唆された。 大胆個体と慎重個体の各脳領域における神経活動活性をEgr1遺伝子の発現量を指標に比較したところ、AVT神経細胞が局在するgPOA領域の他にも、終脳の扁桃体に相当するVs領域を含む複数の脳領域においても、Egr1発現量に差がみられた。これらの終脳領域には、AVT神経の投射領域に加えて、ドーパミン神経の細胞体局在領域も含まれることがわかっている。さらに、Vs領域およびgPOA領域に局在するドーパミン神経の細胞体には、AVT受容体(V1A型)が発現することを確認した。これらの結果から、AVT神経およびドーパミン神経の活動や相互の神経連絡が、メダカにおける大胆または慎重行動の選択に影響する可能性が示唆された。
- 日本学術振興会:科学研究費助成事業 基盤研究(C)研究期間 : 2018年04月 -2021年03月代表者 : 加川 尚本研究は魚類の社会性行動が、成長に伴っていつ発現しどのように発達するのか、また、社会性の発現・発達に、神経ペプチドホルモンがどのような役割を果たすのか解明することを目的としている。H30年度の実験では、メダカの稚魚から成魚に至るまでの各成長段階において、社会性行動の一つである群れ行動はふ化後4週齢頃からみられ始め、その後8週齢までに成魚と同レベルの群れ形成をとるようになること、また、神経ペプチドホルモンであるアルギニンバソトシン(AVT)の脳内発現量は8週齢ではすでに成魚と同レベルであることを明らかにした。このように、ふ化後4~8週齢の期間が群れ形成の発現に重要な時期であることが示されたことから、H31(R1)年度は、ふ化後4~8週の間、群れから隔離飼育した個体を準備し、この隔離飼育個体が他の同体サイズの通常飼育個体に対してどのような群れ行動をとるか調べた。その結果、隔離飼育個体では通常飼育個体と比べて、他個体との個体間距離が長く、他個体への接触回数が少なくなることが明らかとなった。 次に、隔離飼育個体の脳内AVTおよびAVT受容体の遺伝子発現量をリアルタイムPCR法により解析したところ、通常飼育個体と比べてAVTの発現量が有意に低いことがわかった。一方、AVT受容体の発現量は隔離飼育と通常飼育との間で差はみられなかった。 以上のことから、本年度はメダカ稚魚において群れ行動発現期での隔離飼育は他個体との群れ形成に異常をもたらすことを明らかにした。また、この群れ行動異常に稚幼魚期における脳内AVT発現が深く関連することが示唆された。
- 日本学術振興会:科学研究費助成事業 基盤研究(C)研究期間 : 2015年04月 -2018年03月代表者 : 竹垣 毅; 阿見彌 典子; 加川 尚; 松本 有記雄; 中武 洋佑(1-1)ロウソクギンポ雄のMCH(メラニン凝集ホルモン)に摂食を抑制する傾向があったが、全卵食中の雄と摂食中の保護雄のMCHに差はなかった。(1-2)PRL放出刺激ホルモン(PrRP)投与実験では繁殖期に摂食抑制効果が示された。また給餌すると保護雄の保護行動が増加したことから、プロラクチン仮説が支持された。(2)全卵食誘発実験で、全卵食中の雄の11-KTは全卵食しなかった雄よりも有意に低かったことから、雄は11-KTが下がり求愛できなくなると全卵食することが示唆された。(3)卵海水を曝露すると無保護雄に保護行動が誘起されたため、卵の化学物質が保護行動を誘起する刺激である可能性が示唆された。
- 文部科学省:科学研究費補助金(基盤研究(C))研究期間 : 2015年04月 -2018年03月代表者 : 加川 尚本研究ではメダカを用いて雄間競争時に攻撃行動をとる優位個体と逃避行動をとる劣位個体の神経ペプチドホルモン(バソトシン)の脳内作用機構を明らかにすることを試みた。優位個体と劣位個体において、バソトシンを高発現する神経の軸索の脳内投射領域が異なることが分かった。また、それぞれの軸索投射領域では、異なるサブタイプのバソトシン受容体が高発現することが明らかになった。さらに、これらの受容体のうち1つのサブタイプの遺伝子をノックアウトしたメダカを用いて2個体間の雄間競争を観察したところ、いずれの個体も高い攻撃性を示し、競争の決着がつかなくなる傾向がみられた。
- 日本学術振興会:科学研究費助成事業 基盤研究(C)研究期間 : 2012年04月 -2015年03月代表者 : 藤川 和男; 長尾 哲二; 加川 尚実験動物の胎児における核分裂中性子の変異原性効果を明らかにするため,Dlb-1座のヘテロ接合マウスの器官形成期胎児に対する核分裂中性子,高線量率X線および低線量率ガンマ線の照射実験を行った。比較のため、ICR系統の胎児を用いて,外表奇形と未熟赤血球における小核形成を指標として催奇形性と染色体損傷性も調べた。調べたいずれの指標についても、誘発効率は核分裂中性子>X線>がンマ線であった。奇形のX線誘発でみられた顕著な照射時期依存性と対照的に,いずれの放射線についても、器官形成期の2時点で求めた突然変異誘発率は有意差を示さず、器官形成期の間、ほぼ一定の突然変異感受性をもっていることが示唆された。
- 日本学術振興会:科学研究費助成事業 基盤研究(C)研究期間 : 2012年04月 -2015年03月代表者 : 竹垣 毅; 征矢野 清; 加川 尚; 阿見繭 典子; 松本 有記雄; 井手 勇旗; 寺田 龍介; 河南 遙香(1)ロウソクギンポ雄の繁殖サイクルを調節する性ホルモン・アンドロジェン(テストステロン:T)には免疫機能を低下させる効果はなかった。子の保護行動に関与するとされる脳下垂体ホルモン・プロラクチン(PRL)の塩基配列を決定した。(2)巣内の卵操作実験から、卵の存在が繁殖フェイズを切り替えるカギ刺激であることが強く示唆された。(3)体コンディションと卵食数の関係から、全卵食の目的が栄養摂取ではなく卵の存在を消すことにある可能性が示唆された。(4)全卵食行動と摂食行動を区別するために、脳内ペプチドホルモン・ニューロペプチド-Y(NPY)とオレキシン(ORX)の摂食活性への効果を検討した。
- 日本学術振興会:科学研究費助成事業 基盤研究(C)研究期間 : 2010年 -2012年代表者 : 長尾 哲二; 加川 尚合成エストロゲンの胎生期曝露による継世代影響の要因のひとつとして生殖細胞に生じたゲノムワイドなDNAメチル化状態の変化およびインプリンティング遺伝子のDNAメチル化パターンの変化を明らかにした。胎生期の生殖細胞は合成エストロゲン剤によるエピジェネティックな変化を受けやすい時期にあると考えられるが、環境化学物質がどのようなメカニズムでDNAメチル化の変化を誘発するのか、さらに誘発されたDNAメチル化異常が継世代催奇形効果とどのように関連するかは次の課題である。
- 文部科学省:科学研究費補助金(若手研究(B))研究期間 : 2004年 -2006年代表者 : 加川 尚本研究は、異なる種族の野生型メダカ(北日本集団および南日本集団)を用いて、魚類のなわばり行動すなわち他個体への攻撃行動の誘発に関連する新たな生体内因子を探索することを目的として実施した。材料には、従来から研究代表者が飼育維持してきた北日本集団(新潟産)および南日本集団(奈良産)のクローズドコロニーを用いた。昨年度までに、雌雄共に奈良産の方が新潟産に比べて高い攻撃性を有することを明らかにした。また、安静な条件下で単独飼育した奈良産および新潟産の脳視索前野におけるアルギニンバソトシン(AVT)含有ニューロン数が奈良産の方で新潟産に比べて多いことを明らかにした。視索前野におけるAVT発現は、鳥類や両生類において攻撃行動に深く関与することが報告されている。そこで本年度は、両種族の攻撃行動に際する視索前野AVT含有ニューロンの動態について精査した。実験では、雄の奈良産または新潟産をそれぞれ個別に3日間馴化後、共通の標的であるヒメダカ雄と混合飼育し、ヒメダカに対する攻撃行動を観察するとともに、混合飼育直後の脳視索前野におけるAVT含有ニューロン数および細胞体サイズを計測した。その結果、奈良産では、攻撃行動回数およびAVT含有ニューロンの数ならびに細胞体サイズのいずれにおいても新潟産に比べて約2倍高い値を示した。この際、AVT含有ニューロン数は安静時とほぼ同値であったが、安静時には認められなかった顕著に大きい細胞体サイズを有するAVT含有ニューロンが確認された。以上の結果は、ニホンメダカ種族間における攻撃性の違いに、脳視索前野のAVTニューロン細胞体サイズの違いが深く関連することを示唆している。
- 魚類のストレス応答に関する分子機構日本学術振興会:研究期間 : 1999年04月 -2002年03月