Establishment of tools for assessing the effect of endocrine-disrupting chemicals on brain development in non-human primates

• Project/Area Number: 20681005
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Aoyama Gakuin University
• Principal Investigator: NEGISHI Takayuki Aoyama Gakuin University, 理工学部, 助教 (80453489)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000); Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2009: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2008: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: 内分泌かく乱物質 / カニクイザル / ラット / 甲状腺ホルモン / 水酸化PCB / 神経発達

Research Abstract

This study aimed to establish effective tools for assessing the effect of endocrine-disrupting chemicals on brain development in cynomolgus monkey, because cynomolgus monkey is phylogenetically close to human. This study revealed that development of inhibitory neurotransmission system delayed by systemic reduction of thyroid hormone induced by thyroid hormone synthesis inhibitor (methimazole) injection from three to 60 days after birth, when neural development dramatically proceeded. And this study established some in vitro tools using neural cells derived from cynomolgus monkey for assessing the effect of endocrine-disrupting chemicals on brain development

Research Products

• [Journal Article] Maternal plasma polychlorinated biphenyl levels in cynomolgus monkeys (Macaca fascicularis) affect infant social skills in mother-infant interaction. (2011)
  • Author(s): Nakagami A, Koyama T, Kawasaki K, Negishi T, Ihara T, Kuroda Y, Yoshikawa Y.
  • Journal Title: Dev Psychobiol Volume: 53 Pages: 79-88
  • Peer Reviewed
• [Journal Article] Maternal plasma polychlorinated biphenyl levels in cynomolgus monkeys (Macaca fascicularis) affect infant social skills in mother-infant interaction. (2010)
  • Author(s): Nakagami A, Koyama T, Kawasaki K, Negishi T, Ihara T, Kuroda Y, Yoshikawa Y.
  • Journal Title: Developmental Psychobiology. 53 Pages: 79-88
  • Peer Reviewed
• [Journal Article] Enhanced Inhibitory Effects of TBT Chloride on the Development of F(1) Rats. (2010)
  • Author(s): Asakawa H, Tsunoda M, Kaido T, Hosokawa M, Sugaya C, Inoue Y, Kudo Y, Satoh T, Katagiri H, Akita H, Saji M, Wakasa M, Negishi T, Tashiro T, Aizawa Y.
  • Journal Title: Archives of Environmental Contamination and Toxicology. 58 Pages: 1065-1073
  • Peer Reviewed
• [Journal Article] Enhanced Inhibitory Effects of TBT Chloride on the Development of F(1) Rats. (2010)
  • Author(s): Asakawa H, Tsunoda M, Kaido T, Hosokawa M, Sugaya C, Inoue Y, Kudo Y, Satoh T, Katagiri H, Akita H, Saji M, Wakasa M, Negishi T, Tashiro T, Aizawa Y.
  • Journal Title: Arch Environ Contam Toxicol (In press)
  • Peer Reviewed
• [Journal Article] Dynein dysfunction induces endocytic pathology accompanied by an increase in Rab GTPases : a potential mechanism underlying age-dependent endocytic dysfunction. (2009)
  • Author(s): Kimura N, Inoue M, Okabayashi S, Ono F, Negishi T.
  • Journal Title: Journal of Biological Chemistry. 284 Pages: 31291-31302
  • Peer Reviewed
• [Journal Article] Alterations in male infant behaviors towards its mother by prenatal exposure to bisphenol A in cynomolgus monkeys (Macaca fascicularis) during early suckling period. (2009)
  • Author(s): Nakagami A, Negishi T (equal first-author), Kawasaki K, Imai N, Nishida Y, Ihara T, Kuroda Y, Yoshikawa Y, Koyama T.
  • Journal Title: Psychoneuroendocrinology. 34 Pages: 1189-1197
  • Peer Reviewed
• [Journal Article] Alterations in gene expression of glutamate receptors and exocytosis-related factors by a hydroxylated-polychlorinated biphenyl in the developing rat brain. (2009)
  • Author(s): Takahashi M, Negishi T, Imamura M, Sawano E, Kuroda Y, Yoshikawa Y, Tashiro T.
  • Journal Title: Toxicology. 257 Pages: 17-24
  • Peer Reviewed
• [Journal Article] Dynein dysfunction induces endocytic pathology accompanied by an increase in Rab GTPases : a potential mechanism underlying age-dependent endocytic dysfunction. (2009)
  • Author(s): Kimura N, Inoue M, Okabayashi S, Ono F, Negishi T.
  • Journal Title: J Biol Chem 284 Pages: 31291-302
  • Peer Reviewed
• [Journal Article] Alterations in male infant behaviors towards its mother by prenatal exposure to bisphenol A in cynomolgus monkeys (Macaca fascicularis) during early suckling period. (2009)
  • Author(s): Nakagami A, Negishi T, Kawasaki K, Imai N, Nishida Y, Ihara T, Kuroda Y, Yoshikawa Y, Koyama T.
  • Journal Title: Psychoneuroendocrinology 34 Pages: 1189-97
  • Peer Reviewed
• [Journal Article] Alterations in male infant behaviors towards its mother by prenatal exposure to bisphenol A in cynomolgus monkeys (Macaca fascicularis) during early suckling period (2009)
  • Author(s): Nakagami A, Negishi T, Kawasaki K, Imai N, Nishida Y, Ihara T, Kuroda Y, Yoshikawa Y, Kovama T.
  • Journal Title: Psychoneuroendocrinology (In press)
  • Peer Reviewed
• [Journal Article] Distribution and Excretion of Arsenic in Cynomolgus Monkey Following Repeated Administration of Diphenylarsinic Acid. (2008)
  • Author(s): Kobayashi Y, Negishi T, Mizumura A, Watanabe T, Hirano S.
  • Journal Title: Archives of Toxicology. 82 Pages: 553-561
  • Peer Reviewed
• [Journal Article] Identification of genes mediating thyroid hormone action in the developing mouse cerebellum. (2008)
  • Author(s): Takahashi M, Negishi T, Tashiro T.
  • Journal Title: Journal of Neurochemistry. 104 Pages: 640-652
  • Peer Reviewed
• [Journal Article] Genetic manipulation of brain cultures from the primates : a novel tool for molecular studies of neuropsychiatric disorders. (2008)
  • Author(s): Yasumoto F, Hayashi A, Kamiya A, Negishi T, Yoshikawa Y, Sawa A.
  • Journal Title: Molecular Psychiatry. 13 Pages: 116-118
  • Peer Reviewed
• [Journal Article] Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid (2008)
  • Author(s): Kobayashi Y, Negishi T, Mizumura A, Watanabe T, Hirano S.
  • Journal Title: Archives of Toxicology 82 Pages: 553-561
  • Peer Reviewed
• [Journal Article] Alterations in gene expression of glutamate receptors anc exocytosis-related factors by a hydroxylated-polychlorinated biphenyl in the developing rat Brain (2008)
  • Author(s): Takahashi M, Negishi T, Imamura M, Sawano E, Kuroda Y, Yoshikawa Y, Tashiro T.
  • Journal Title: Toxicology 257 Pages: 17-24
  • Peer Reviewed
• [Presentation] THE EFFECT OF PRENATAL EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS (EDCS) ON THE DEVELOPMENT OF MACAQUE SOCIALIZATION. (2010)
  • Author(s): Nakagami A, Negishi T, Kawasaki K, Kuroda Y, Yoshikawa Y, Koyama T.
  • Organizer: International Primatological Society XXIII Congress Kyoto 2010
  • Place of Presentation: Kyoto University, Kyoto, Japan
  • Year and Date: 2010-12-16
• [Presentation] Effects of thyroid hormone on the survival and neurite outgrowth of cultured cerebellar granule cells (2010)
  • Author(s): K.Oyanagi, T.Negishi, T.Tashiro
  • Organizer: The 10th biennial meeting of the ASIA-PACIFIC SOCIETY FOR NEUROCHEMISTRY
  • Place of Presentation: Phuket, Thailand
  • Year and Date: 2010-10-19
• [Presentation] Investigation of cerebral development in cynomolgus monkey - Histological and biochemical analyses (2010)
  • Author(s): T.Negishi, K.Oyanagi, M.Takahashi, N.Imai, T.Ihara, T.Tashiro
  • Organizer: The 10th biennial meeting of the ASIA-PACIFIC SOCIETY FOR NEUROCHEMISTRY
  • Place of Presentation: Phuket, Thailand
  • Year and Date: 2010-10-18
• [Presentation] Local thyroid hormone matabolism in the hippocampus of senescence-accelerated SAMP8 mice (2010)
  • Author(s): E.Sawano, T.Negishi, T.Tashiro
  • Organizer: The 10th biennial meeting of the ASIA-PACIFIC SOCIETY FOR NEUROCHEMISTRY
  • Place of Presentation: Phuket, Thailand
  • Year and Date: 2010-10-18
• [Presentation] Analysis of gene expression profiles in the hippocampus and cerebellum of the Goto-Kakizaki rat, an animal model of type 2 diabetes (2010)
  • Author(s): T.Uno, Y.Ishibashi, M.Takahashi, T.Negishi, T.Tashiro
  • Organizer: The 10th biennial meeting of the ASIA-PACIFIC SOCIETY FOR NEUROCHEMISTRY
  • Place of Presentation: Phuket, Thailand
  • Year and Date: 2010-10-18
• [Presentation] Investigation of cerebral development in cynomolgus monkey-Histological and biochemical analyses (2010)
  • Author(s): T.Negishi, K.Oyanagi, M.Takahashi, N.Imai, T.Ihara, T.Tashiro
  • Organizer: The 10th biennial meeting of the ASIA-PACIFIC SOCIETY FOR NEUROCHEMISTRY
  • Place of Presentation: Phuket, Thaiand
  • Year and Date: 2010-10-18
• [Presentation] Local thyroid hormone matabolism in the hippocampus of senescence-accelerated SAMP8 mice (2010)
  • Author(s): E.Sawano, T.Negishi, T.Tashiro
  • Organizer: The 10th biennial meeting of the ASIA-PACIFIC SOCIETY FOR NEUROCHEMISTRY
  • Place of Presentation: Phuket, Thaiand
  • Year and Date: 2010-10-18
• [Presentation] Diphenylarsinic acid induced oxidative stress and expression of neuroactive and vasoactive peptides in cerebellar astrocytes (2010)
  • Author(s): Takayuki Negishi, Masaki Takahashi, Kohshi Oyanagi, Hiroaki Ohnishi, Seishiro Hirano, Tomoko Tashiro
  • Organizer: Neuro2010
  • Place of Presentation: 神戸、神戸コンベンションセンター(国際会議場・国際展示場)
  • Year and Date: 2010-09-04
• [Presentation] Perinatal exposure affects the sensitivity to TBT neurotoxicity after maturation : evaluation by gene expression and behavioral analyses (2010)
  • Author(s): Masashi Tsunoda, Yuki Takeuchi, Ryousuke Yoshioka, Takayuki Negishi, Ryutaro Ikeuchi, Takaya Kaido, Mayuko Hosokawa, Chiemi Sugaya, Tomoko Tashiro, Yoshiharu Aizawa
  • Organizer: Neuro2010
  • Place of Presentation: 神戸、神戸コンベンションセンター(国際会議場・国際展示場)
  • Year and Date: 2010-09-04
• [Presentation] Diphenylarsinic acid induced oxidative stress and expression of neuroactive and vasoactive peptides in cerebellar astrocytes (2010)
  • Author(s): Takayuki Negishi, Masaki Takahashi, Kohshi Oyanagi, Hiroaki Ohnishi, Seishiro Hirano, Tomoko Tashiro
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-04
• [Presentation] Perinatal exposure affects the sensitivity to TBT neurotoxicity after maturation : evaluation by gene expression and behavioral analyses (2010)
  • Author(s): Masashi Tsunoda, Yuki Takeuchi, Ryousuke Yoshioka, Takayuki Negishi, Ryutaro Ikeuchi, Takaya Kaido, Mayuko Hosokawa, Chiemi Sugaya, Tomoko Tashiro, Yoshiharu Aizawa
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-04
• [Presentation] Non-genomic action of Thyroxine (T4) on survival and neurite outgrowth of cerebellar granule cells in culture (2010)
  • Author(s): Koshi Oyanagi, Takayuki Negishi, Tomoko Tashiro
  • Organizer: Neuro2010
  • Place of Presentation: 神戸、神戸コンベンションセンター(国際会議場・国際展示場)
  • Year and Date: 2010-09-03
• [Presentation] Alterations in local thyroid hormone metabolism in the hippocampus of senescence-accelerated SAMP8 mice (2010)
  • Author(s): Erika Sawano, Takayuki Negishi, Tomoko Tashiro
  • Organizer: Neuro2010
  • Place of Presentation: 神戸、神戸コンベンションセンター(国際会議場・国際展示場)
  • Year and Date: 2010-09-03
• [Presentation] Non-genomic action of Thyroxine (T4) on survival and neurite outgrowth of cerebellar granule cells in culture (2010)
  • Author(s): Koshi Oyanagi, Takayuki Negishi, Tomoko Tashiro
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-03
• [Presentation] Alterations in local thyroid hormone metabolism in the hippocampus of senescence-accelerated SAMP8 mice (2010)
  • Author(s): Erika Sawano, Takayuki Negishi, Tomoko Tashiro
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-03
• [Presentation] Traffic Jam hypothesis: dynein dysfunction causes endocytic pathology leading to intracellular Aβaccumulation. (2010)
  • Author(s): Nobuyuki Kimura, Makoto Inoue, Sachi Okabayashi, Fumiko Ono, Takayuki Negishi
  • Organizer: Neuro2010
  • Place of Presentation: 神戸、神戸コンベンションセンター(国際会議場・国際展示場)
  • Year and Date: 2010-09-02
• [Presentation] Traffic Jam hypothesis : dynein dysfunction causes endocytic pathology leading to intracellular Assaccumulation. (2010)
  • Author(s): Nobuyuki Kimura, Makoto Inoue, Sachi Okabayashi, Fumiko Ono, Takayuki Negishi
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-02
• [Presentation] サル類の行動を指標とした胎生期化学物質曝露による神経発達毒性の評価 (2009)
  • Author(s): 根岸隆之
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島県、鹿児島市民文化ホール
  • Year and Date: 2009-06-25
• [Presentation] サル類の行動を指標とした胎生期化学物質曝露による神経発達毒性の評価 (2009)
  • Author(s): 根岸隆之
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島市民文化ホール
  • Year and Date: 2009-06-25
• [Presentation] ラット脳の発達に対するトリブチルスズ曝露の影響に関する二世代トキシコジェノミック研究 (2009)
  • Author(s): 角田正史、若佐美佳、浅川秀雄、高橋理貴、根岸隆之、峡戸孝也、細川まゆ子、菅谷ちえ美、井上葉子、相澤好治、田代朋子
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県、伊香保温泉
  • Year and Date: 2009-06-24
• [Presentation] 小脳顆粒細胞におけるジフェニルアルシン酸による酸化ストレスと細胞死 (2009)
  • Author(s): 根岸隆之、高橋理貴、小柳洸志、大西大空、平野靖史郎、田代朋子
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県、伊香保温泉
  • Year and Date: 2009-06-22
• [Presentation] 培養小脳顆粒細胞における低カリウム誘発細胞死に対する甲状腺ホルモンT4の細胞保護作用 (2009)
  • Author(s): 小柳洸志、高橋理貴、根岸隆之、田代朋子
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県、伊香保温泉
  • Year and Date: 2009-06-22
• [Presentation] GABA神経伝達機構の発達における甲状腺ホルモンの役割 (2009)
  • Author(s): 澤野恵梨香、高橋理貴、船津尚子、木村洋人、根岸隆之、田代朋子
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県、伊香保温泉
  • Year and Date: 2009-06-22
• [Presentation] 2型糖尿病モデル・GKラットの脳におけるホモシステイン代謝の変化 (2009)
  • Author(s): 宇野健史、石橋瑛、高橋理貴、根岸隆之、田代朋子
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県、伊香保温泉
  • Year and Date: 2009-06-22
• [Presentation] メチマゾール短期曝露カニクイザル胎児における脳の組織学的検索 (2008)
  • Author(s): 豊島祐次郎、根岸隆之、伊原敏夫、吉川泰弘
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: 宮崎県、シーガイア・ワールドコンベンションセンター・サミット
  • Year and Date: 2008-09-24
• [Presentation] 初代培養ラット小脳顆粒細胞における低カリウム誘発細胞死に対する内因性グルタミン酸の役割 (2008)
  • Author(s): 小柳洸志、高橋理貴、根岸隆之、田代朋子
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山県、富山国際会議場
  • Year and Date: 2008-09-13
• [Presentation] トリブチルスズ経世代曝露による発達期脳の遺伝子発現変化 (2008)
  • Author(s): 若佐美佳、今村誠、吉岡良祐、高橋理貴、根岸隆之、角田正、相澤好治、田代英夫、田代朋子
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山県、富山国際会議場
  • Year and Date: 2008-09-13
• [Presentation] 初代培養ラット小脳顆粒細胞における低カリウム誘発細胞死に対する内因性グルタミン酸の役割 (2008)
  • Author(s): 小柳洸志、高橋理貴、根岸隆之、田代朋子
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-13
• [Presentation] LPS誘導末梢性炎症による脳内甲状腺ホルモンシステムの変化 (2008)
  • Author(s): 高橋理貴、根岸隆之、澤野恵梨香、田代朋子
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山県、富山国際会議場
  • Year and Date: 2008-09-12