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所属部署医学研究科高度医療教育研究センター
職名准教授(診療担当)
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Last Updated :2020/06/03

研究者基本情報

学歴

  • 1994年04月 - 1997年03月, 名古屋市立大学大学院, 薬学研究科博士課程
  • 1992年04月 - 1994年03月, 名古屋市立大学大学院, 薬学研究科修士課程

学位

  • 博士(薬学), 名古屋市立大学

所属学協会

  • 日本神経科学学会
  • Society for Neuroscience
  • 愛知県病院薬剤師会
  • 日本神経化学会
  • 日本神経精神薬理学会
  • 日本医療薬学会
  • 日本病院薬剤師会
  • 日本生化学会
  • 日本基礎老化学会
  • 日本分子生物学会
  • 日本癌学会
  • 日本薬理学会
  • 日本薬学会

経歴

  •   2018年04月 - 現在, 名古屋市立大学大学院, 医学研究科・薬学研究科, 准教授
  •   2014年04月 - 2018年03月, 名古屋大学医学部附属病院, 薬剤部, 薬剤師
  •   2010年05月 - 2014年03月, 名古屋大学医学部附属病院薬剤部 特任助教
  •   2009年04月01日 - 2010年04月30日, 名古屋大学医学部附属病院薬剤部・大学院医学系研究科医療薬学講座 GCOE特任助教
  •   2007年04月01日 - 2009年03月30日, 平成19年度採用 財団法人長寿科学振興財団 リサーチレジデント(名古屋大学医学部附属病院薬剤部・大学院医学系研究科医療薬学講座)
  •   2005年10月01日 - 2007年03月30日, 国立長寿医療センター研究所再生再建医学研究部 流動研究員
  •   2003年01月01日 - 2005年09月30日, 平成14年度採用 日本学術振興会特別研究員PD(国立長寿医療センター研究所老年病研究部)
  •   2001年08月01日 - 2002年12月31日, 国立長寿医療センター研究所老年病研究部 流動研究員
  •   1997年06月01日 - 2001年07月31日, 名古屋市立大学大学院薬学研究科 助手

研究活動情報

論文

  • Methylation analysis for postpartum depression: a case control study., Nakamura Y, Nakatochi M, Kunimoto S, Okada T, Aleksic B, Toyama M, Shiino T, Morikawa M, Yamauchi A, Yoshimi A, Furukawa-Hibi Y, Nagai T, Ohara M, Kubota C, Yamada K, Ando M, Ozaki N, BMC Psychiatry., 19, (1) ,   2019年06月, 査読有り
  • Association between CYP2C19 genotype and the additional effect of cilostazol to clopidogrel resistance in neuroendovascular therapy., Tajima H, Izumi T, Miyachi S, Matsubara N, Ito M, Imai T, Nishihori M, Shintai K, Okamoto S, Araki Y, Kumakura Y, Furukawa-Hibi Y, Yamada K, Wakabayashi T, Nagoya J Med Sci., 80, (2) 207 - 215,   2018年05月, 査読有り
  • Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in pentylenetetrazole-induced epilepsy through the induction of Homer1a., Shan W, Nagai T, Tanaka M, Itoh N, Furukawa-Hibi Y, Nabeshima T, Sokabe M, Yamada K, Journal of neurochemistry, 145, (1) 19 - 33,   2018年04月, 査読有り
  • Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development, Kazuyuki Sumi, Kyosuke Uno, Hiroshi Noike, Takenori Tomohiro, Yasumaru Hatanaka, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Yoshiaki Miyamoto, Atsumi Nitta, SCIENTIFIC REPORTS, 7, (1) ,   2017年12月, 査読有り, We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati(-/-)) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati(-/-) mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati(-/-) mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.
  • Decreased DNA methylation in the Shati/1 Nat8l promotor in both patients with schizophrenia and a methamphetamine-induced murine model of schizophrenia, Uno K, Kikuchi Y, Uehara T, Matsuoka T, Sumiyoshi T, Furukawa-Hibi Y, Nabeshima T, Miyamoto Y, Nitta A, PLoS One., 11, (6) ,   2016年, 査読有り
  • Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer's disease., Mita T, Furukawa-Hibi Y, Takeuchi H, Hattori H, Yamada K, Hibi H, Ueda M, Yamamoto A, Behavioural brain research, 293, 189 - 197,   2015年10月, 査読有り
  • Induction of neuronal axon outgrowth by Shati/Nat8l by energy metabolism in mice cultured neurons., Kazuyuki Sumi, Kyosuke Uno, Shohei Matsumura, Yoshiaki Miyamoto, Yoko Furukawa-Hibi, Shin-Ichi Muramatsu, Toshitaka Nabeshima, Atsumi Nitta, Neuroreport, 26, (13) 740 - 6,   2015年09月09日, 査読有り, A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens of mice repeatedly treated with methamphetamine (METH). Shati/Nat8l has been reported to inhibit the pharmacological action induced by METH. Shati/Nat8l produces N-acetylaspartate from aspartate and acetyl-CoA. Previously, we reported that overexpression of Shati/Nat8l in nucleus accumbens attenuates the response to METH by N-acetylaspartylglutamate (which is derived from N-acetylaspartate)-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in-situ hybridization for the detection of Shati/Nat8l mRNA along with immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain; then, we used an adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary cultured neurons to investigate the contribution toward the neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary cultured neurons induced axonal growth, but not dendrite elongation at day 1.5 (DIV). This finding indicated that Shati/Nat8l contributes toward neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and N-acetylaspartylglutamate itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth by ATP synthesis and not through mGluR3 signaling.
  • Stress increases DNA methylation of the neuronal PAS domain 4 (Npas4) gene, Yoko Furukawa-Hibi, Taku Nagai, Jaesuk Yun, Kiyofumi Yamada, NEUROREPORT, 26, (14) 827 - 832,   2015年09月, 査読有り, Neuronal Per Arnt Sim domain 4 (Npas4), a brain-specific helix-loop-helix transcription factor, was recently shown to regulate the development of GABAergic inhibitory neurons. Npas4 mRNA expression levels were decreased in the hippocampus of mice exposed to stress, which was accompanied by brain dysfunction. We have suggested that transient stress reduced Npas4 transcription through the glucocorticoid receptor. In the present report, we investigated the potential contribution of epigenetic modifications induced by stress on Npas4 gene expression. The Npas4 promoter region contains two CpG islands; in the hippocampus, chronic restraint stress increases the DNA methylation levels of both of these CpG islands. In the Neuro2a cell line, treatment with a DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine, increased Npas4 mRNA levels and markedly reduced the DNA methylation levels of CpG island 2 in the Npas4 promoter. The DNA methylation sites in CpG island 2 overlap with two cyclic adenosine monophosphate response element (CRE) sequences. Mutation of these CRE sequences reduced Npas4 promoter activity. These results suggest that transcription of the Npas4 gene is downregulated by stress through DNA methylation of its promoter.
  • Practical Program to Gather Patient Information from a Diversified Perspective and Provide Appropriate Therapies in Practical Hospital Training, Tomomi Tsubai, Yukihiro Noda, Yoko Hibi, Akihiro Mouri, Sakiko Nishikawa, Kiyofumi Yamada, Makoto Nakao, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 135, (3) 507 - 518,   2015年03月, 査読有り, In the 11-week practical hospital training of pharmaceutical students in Nagoya University Hospital, a clinical practice program has been implemented with the objective of compensating for any deficits students may have in skills and attitudes due to insufficiencies in their formal education. The program aims to enable the students to observe patients from various angles, obtain from them information necessary for drug therapy, and propose multiple treatment methods according to the patient's background and situation. Tests are conducted before and after the program to assess the students' knowledge and to confirm whether lectures on basic knowledge of practical skills had been provided and whether practical skill training had been performed. The rate of correct answers on the postprogram test rose significantly after the practice program compared with the preprogram scores, thus confirming that the students' knowledge improved. Because the content of their knowledge and the experience that they had acquired previously was in accordance with older guidelines, however, it will be necessary to update students' knowledge regularly and to instill knowledge, skills, and attitudes that they will be able to apply in actual medical practice. In the questionnaire after the end of the program, more than 80% of the students indicated that they had benefitted. Many responded that this program would be useful for their practical hospital training on the wards and for their future work. This suggests that the program is extremely beneficial to the students.
  • Aberrant DNA methylation is associated with a poor outcome in juvenile myelomonocytic leukemia., Sakaguchi H, Muramatsu H, Okuno Y, Makishima H, Xu Y, Furukawa-Hibi Y, Wang X, Narita A, Yoshida K, Shiraishi Y, Doisaki S, Yoshida N, Hama A, Takahashi Y, Yamada K, Miyano S, Ogawa S, Maciejewski JP, Kojima S, PLoS One., 10, (12) ,   2015年, 査読有り
  • Npas4 Regulates Mdm2 and thus Dcx in Experience-Dependent Dendritic Spine Development of Newborn Olfactory Bulb Interneurons, Sei-ichi Yoshihara, Hiroo Takahashi, Nobushiro Nishimura, Masahito Kinoshita, Ryo Asahina, Michiko Kitsuki, Kana Tatsumi, Yoko Furukawa-Hibi, Hirokazu Hirai, Taku Nagai, Kiyofumi Yamada, Akio Tsuboi, CELL REPORTS, 8, (3) 843 - 857,   2014年08月, 査読有り, Sensory experience regulates the development of various brain structures, including the cortex, hippocampus, and olfactory bulb (OB). Little is known about how sensory experience regulates the dendritic spine development of OB interneurons, such as granule cells (GCs), although it is well studied in mitral/tufted cells. Here, we identify a transcription factor, Npas4, which is expressed in OB GCs immediately after sensory input and is required for dendritic spine formation. Npas4 overexpression in OB GCs increases dendritic spine density, even under sensory deprivation, and rescues reduction of dendrite spine density in the Npas4 knockout OB. Furthermore, loss of Npas4 upregulates expression of the E3-ubiquitin ligase Mdm2, which ubiquitinates a microtubule-associated protein Dcx. This leads to reduction in the dendritic spine density of OB GCs. Together, these findings suggest that Npas4 regulates Mdm2 expression to ubiquitinate and degrade Dcx during dendritic spine development in newborn OB GCs after sensory experience.
  • Overexpression of Shati/Nat8l, an N-acetyltransferase, in the nucleus accumbens attenuates the response to methamphetamine via activation of group II mGluRs in mice, Yoshiaki Miyamoto, Yudai Ishikawa, Noriyuki Iegaki, Kazuyuki Sumi, Kequan Fu, Keiji Sato, Yoko Furukawa-Hibi, Shin-ichi Muramatsu, Toshitaka Nabeshima, Kyosuke Uno, Atsumi Nitta, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 17, (8) 1283 - 1294,   2014年08月, 査読有り, A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens (NAc) of mice with methamphetamine (METH) treatment. Previously we reported that suppression of Shati/Nat8l enhanced METH-induced behavioral alterations via dopaminergic neuronal regulation. However, the physiological mechanisms of Shati/Nat8l on the dopaminergic system in the brain are unclear. In this study, we injected adeno-associated virus (AAV) vector containing Shati/Nat8l into the NAc or dorsal striatum (dS) of mice, to increase Shati/Nat8l expression. Overexpression of Shati/Nat8l in the NAc, but not in the dS, attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference in mice. Moreover, the Shati/Nat8l overexpression in the NAc attenuated the elevation of extracellular dopamine levels induced by METH in in vivo microdialysis experiments. These behavioral and neurochemical alterations due to Shati/Nat8l overexpression in the NAc were inhibited by treatment with selective group II metabotropic glutamate receptor type 2 and 3 (mGluR2/3) antagonist LY341495. In the AAV vector-injected NAc, the tissue contents of both N-acetylaspartate and N-acetylaspartylglutamate (NAAG), endogenous mGluR3 agonist, were elevated. The injection of peptidase inhibitor of NAAG or the perfusion of NAAG itself reduced the basal levels of extracellular dopamine in the NAc of naive mice. These results indicate that Shati/Nat8l in the NAc, but not in the dS, plays an important suppressive role in the behavioral responses to METH by controlling the dopaminergic system via activation of group II mGluRs.
  • Alteration of gene expression and DNA methylation in drug-resistant gastric cancer, Osamu Maeda, Takafumi Ando, Naoki Ohmiya, Kazuhiro Ishiguro, Osamu Watanabe, Ryoji Miyahara, Yoko Hibi, Taku Nagai, Kiyofumi Yamada, Hidemi Goto, ONCOLOGY REPORTS, 31, (4) 1883 - 1890,   2014年04月, 査読有り, The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)- and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were established with culture for >10 months in a medium containing 5-FU or CDDP. Endoscopic biopsy specimens were obtained from gastric cancer patients who underwent chemotherapy with oral fluoropyrimidine S-1 and CDDP. Gene expression and DNA methylation analyses were performed using microarray, and validated using real-time PCR and pyrosequencing, respectively. Out of 17,933 genes, 541 genes commonly increased and 569 genes decreased in both 5-FU- and CDDP-resistant AGS cells. Genes with expression changed by drugs were related to GO term 'extracellular region' and 'p53 signaling pathway' in both 5-FU- and CDDP-treated cells. Expression of 15 genes including KLK13 increased and 12 genes including ETV7 decreased, in both drug-resistant cells and biopsy specimens of two patients after chemotherapy. Out of 10,365 genes evaluated with both expression microarray and methylation microarray, 74 genes were hypermethylated and downregulated, or hypomethylated and upregulated in either 5-FU-resistant or CDDP-resistant cells. Of these genes, expression of 21 genes including FSCN1, CPT1C and NOTCH3, increased from treatment with a demethylating agent. There are alterations of gene expression and DNA methylation in drug-resistant gastric cancer; they may be related to mechanisms of drug resistance and may be useful as biomarkers of gastric cancer drug sensitivity.
  • Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence., Kazuya Toriumi, Mizuki Kondo, Taku Nagai, Ryota Hashimoto, Kazutaka Ohi, Ziyu Song, Junko Tanaka, Akihiro Mouri, Takenao Koseki, Hidenaga Yamamori, Yoko Furukawa-Hibi, Takayoshi Mamiya, Takeshi Fukushima, Masatoshi Takeda, Atsumi Nitta, Kiyofumi Yamada, Toshitaka Nabeshima, The international journal of neuropsychopharmacology, 17, (3) 443 - 53,   2014年03月, 査読有り, In a previous report, we identified a novel molecule, SHATI/NAT8L, having an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). SHATI/NAT8L attenuates the METH-induced increase in dopamine overflow in the nucleus accumbens (NAc) by promoting plasmalemmal and vesicular dopamine uptake. However, the biological functions of the protein remain unclear. In this study, we explored NAT8L-binding proteins using pull-down assays and identified a number of components of the adaptor protein (AP)-2 complex, which is a multimeric protein localized to the plasma membrane that functions to internalize cargo during clathrin-mediated endocytosis. To investigate whether NAT8L regulates the receptor localization to the cell surface, cell-surface dopamine D1 receptor in the NAc of Nat8l knockout (KO) mice was quantified. We found that dopamine D1 receptor on the cell surface was increased in the NAc of Nat8l KO mice compared with the wild type (WT) animals. Consistent with this finding, Nat8l KO mice showed higher basal locomotor activity and heightened sensitivity to D1 agonist compared with WT mice. In addition, METH-induced sensitization and CPP were enhanced in Nat8l KO mice. These results suggest that NAT8L might regulate the localization of cell-surface dopamine D1 receptor, thereby controlling basal behaviour and sensitivity to METH. Furthermore, we observed a single nucleotide polymorphism (SNP) in the human NAT8L gene related to reward dependence, a personality trait, and grey matter volume in the caudate nucleus in healthy subjects, suggesting that NAT8L might also affect human personality.
  • Correlation of CYP2C19 Phenotype With Voriconazole Plasma Concentration in Children, Atsushi Narita, Hideki Muramatsu, Hirotoshi Sakaguchi, Sayoko Doisaki, Makito Tanaka, Asahito Hama, Akira Shimada, Yoshiyuki Takahashi, Nao Yoshida, Kimikazu Matsumoto, Koji Kato, Kazuko Kudo, Yoko Furukawa-Hibi, Kiyofumi Yamada, Seiji Kojima, JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 35, (5) E219 - E223,   2013年07月, 査読有り, Background: Voriconazole is a triazole antifungal agent with potent activity against a broad spectrum of pathogens, including Aspergillus and Candida species. In human adults, allelic polymorphisms of CYP2C19 are known to correlate with significant variation in voriconazole plasma concentration. Here, we report an analysis of CYP2C19 phenotype and voriconazole plasma concentrations in children. Methods: This retrospective study included 37 children who had voriconazole plasma concentrations measured from May 2006 to June 2011. All had single-nucleotide polymorphisms that define the 3 major CYP2C19 alleles. Patients were classified as follows: normal metabolizers, intermediate metabolizers, poor metabolizers, or hypermetabolizers. Results: The frequencies of the 3 CYP2C19 genetic polymorphisms were similar to those previously reported for Japanese adults. Trough plasma concentrations of voriconazole were significantly higher in the poor metabolizer and intermediate metabolizer groups compared with the normal metabolizer and hypermetabolizer groups (P=0.004). Two patients with high plasma concentrations experienced voriconazole-related severe adverse events (syndrome of inappropriate antidiuretic hormone secretion and cardiac toxicities). Conclusions: The current study suggests that a significant association exists in children between the voriconazole plasma concentration and the CYP2C19 phenotype. Dose adjustment based on CYP2C19 phenotype may be useful during voriconazole therapy, especially for Japanese children, who as a group have a higher incidence of the poor metabolizer and intermediate metabolizer phenotypes.
  • SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization., Toriumi K, Ikami M, Mouri A, Koseki T, Ibi D, Furukawa-Hibi Y, Nagai T, Mamiya T, Nitta A, Yamada K, Nabeshima T, J. Neurosci. Res., 91, (12) 1525 - 1532,   2013年, 査読有り
  • Neuronal Per Arnt Sim (PAS) Domain Protein 4 (NPAS4) Regulates Neurite Outgrowth and Phosphorylation of Synapsin I, Jaesuk Yun, Taku Nagai, Yoko Furukawa-Hibi, Keisuke Kuroda, Kozo Kaibuchi, Michael E. Greenberg, Kiyofumi Yamada, JOURNAL OF BIOLOGICAL CHEMISTRY, 288, (4) 2655 - 2664,   2013年01月, 査読有り, Neuronal Per Arnt Sim domain protein 4 (NPAS4), a brain-specific basic helix-loop-helix transcription factor, has recently been shown to regulate the development of the GABAergic inhibitory synapses and transcription program for contextual memory formation in the hippocampus. We previously reported that chronic social isolation or restriction stress in mice resulted in an impairment in memory and emotional behavior, which was associated with a decrease in Npas4 mRNA levels. In this study, we investigated the role of NPAS4 in neuronal function in vitro and in vivo. Differentiation medium-induced neurite outgrowth was inhibited in Npas4 knockdown Neuro2a cells, whereas overexpression of NPAS4 accelerated the neurite outgrowth in Neuro2a cells. Furthermore, depolarization-induced neurite outgrowth was abolished in Npas4 KO hippocampal neurons. NPAS4 overexpression increased cyclin-dependent kinase 5 (CDK5)-dependent synapsin I phosphorylation in Neuro2a cells and primary cultured hippocampal neurons. A CDK5 inhibitor, roscovitine, inhibited the neurite outgrowth and the increase in phosphorylated synapsin I (p-SYN I) levels in Npas4-overexpressed Neuro2a cells. Interaction of NPAS4 with promoters of Cdk5 and NeuN genes was demonstrated by a chromatin immunoprecipitation assay. In an in vivo study, pentylenetetrazole-induced convulsions in mice resulted in an increase in NPAS4 and p-SYN I levels in the prefrontal cortex of wild-type mice, although no changes in p-SYN I levels were observed in Npas4 knock-out mice. These results suggest that NPAS4 plays an important role in the structural and functional plasticity of neurons.
  • Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter, Yoko Furukawa-Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, JOURNAL OF NEUROCHEMISTRY, 123, (5) 866 - 875,   2012年12月, 査読有り, Neuronal PAS domain 4 (NPAS4), a brain-specific helixloophelix transcription factor, has recently been shown to regulate the development of GABAergic inhibitory neurons. We previously reported that Npas4 mRNA expression levels were reduced in the hippocampus of mice exposed to social isolation or restraint stress, which was accompanied by impairment of memory, emotional behavior, and hippocampal neurogenesis. Therefore, the reduction of NPAS4 expression may play a role in stress-induced brain dysfunction. In this study, to investigate the transcriptional regulation of Npas4 by stress, we focused on the effect of glucocorticoids (GCs) upon Npas4 transcription. Corticosterone treatment reduced Npas4 expression in the frontal cortex and hippocampus, whereas adrenalectomy caused an increase in expression. GC receptor (GR) antagonist, mifepristone, inhibited the stress-induced reduction of Npas4 expression. Putative negative glucocorticoid response elements (GREs) were found -2000 to -1000 upstream of the Npas4 transcription initiation site. Npas4 promoter activity was increased by mifepristone or by mutation of the negative GRE sequences. A chromatin immunoprecipitation assay revealed that restraint stress increased the binding of GR to Npas4 promoter region in the hippocampus. These results suggest that transcription of Npas4 is down-regulated by stress via the binding of agonist-bound GR to its promoter.
  • Absence of SHATI/Nat8l reduces social interaction in mice, Yoko Furukawa-Hibi, Atsumi Nitta, Hidefumi Fukumitsu, Hitomi Somiya, Kazuya Toriumi, Shoei Furukawa, Toshitaka Nabeshima, Kiyofumi Yamada, NEUROSCIENCE LETTERS, 526, (2) 79 - 84,   2012年09月, 査読有り, We previously identified a novel molecule "Shati/Nat8l" from the nucleus accumbens of mice. However, the physiological roles of the SHATI protein are not clear. To investigate the effect of SHATI on the central nervous system and behavior, we studied knockout mice of this protein. We carried out various behavior tests using Shari-knockout mice. Shati-knockout mice did not differ from wild type mice in learning and memory. In the open field test, Shari-knockout mice did not differ from wild-type mice in time of stay in the outer, middle and center areas. On the other hand, Shari-knockout mice showed increases in rearing and grooming time in the open field test, and exploration time of novel objects. These results suggested that knockout of the Shari gene may increase exploration in specific circumstances. Interestingly, the Shati-knockout mice avoided social interaction with unfamiliar mice out of their home cage, although there was no difference in social interaction in their home cage compared with wild type mice. Lack of the Shari gene increased brain-derived neurotrophic factor (BDNF) mRNA in the prefrontal cortex and hippocampus, and decreased glial cell line-derived neurotrophic factor (GDNF) mRNA in the striatum and hippocampus, and lipopolysaccharides-induced TNF-alpha factor (LITAF) mRNA in the striatum. Since these factors play important roles in behavior, alteration of expression of these factors may be related to the induction of exploration and reduction of social interaction in Shari-knockout mice. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia, Sayoko Doisaki, Hideki Muramatsu, Akira Shimada, Yoshiyuki Takahashi, Makiko Mori-Ezaki, Masanori Sato, Hiroyuki Kawaguchi, Akitoshi Kinoshita, Manabu Sotomatsu, Yasuhide Hayashi, Yoko Furukawa-Hibi, Kiyofumi Yamada, Hideaki Hoshino, Hitoshi Kiyoi, Nao Yoshida, Hirotoshi Sakaguchi, Atsushi Narita, Xinan Wang, Olfat Ismael, Yinyan Xu, Nobuhiro Nishio, Makito Tanaka, Asahito Hama, Kenichi Koike, Seiji Kojima, BLOOD, 120, (7) 1485 - 1488,   2012年08月, 査読有り, Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. Somatic mutations in genes involved in GM-CSF signal transduction, such as NRAS, KRAS, PTPN11, NF1, and CBL, have been identified in more than 70% of children with JMML. In the present study, we report 2 patients with somatic mosaicism for oncogenic NRAS mutations (G12D and G12S) associated with the development of JMML. The mutated allele frequencies quantified by pyrosequencing were various and ranged from 3%-50% in BM and other somatic cells (ie, buccal smear cells, hair bulbs, or nails). Both patients experienced spontaneous improvement of clinical symptoms and leukocytosis due to JMML without hematopoietic stem cell transplantation. These patients are the first reported to have somatic mosaicism for oncogenic NRAS mutations. The clinical course of these patients suggests that NRAS mosaicism may be associated with a mild disease phenotype in JMML. (Blood. 2012;120(7):1485-1488)
  • [Functional analysis of stress-responsible transcription factor Npas4 in stress-induced brain dysfunction]., Nagai T, Yun J, Ibi D, Koike H, Hibi Y, Yamada K, Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 139, (4) 147 - 151,   2012年04月, 査読有り
  • Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome, Chisako Iriyama, Akihiro Tomita, Hideaki Hoshino, Mizuho Adachi-Shirahata, Yoko Furukawa-Hibi, Kiyofumi Yamada, Hitoshi Kiyoi, Tomoki Naoe, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 419, (4) 662 - 669,   2012年03月, 査読有り, Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities. BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3-9) using DNAs from plasma, serum, and PB mononuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic/epigenetic analyses using PB circulating DNA can be a safer and painless alternative to using BM cells. (C) 2012 Elsevier Inc. All rights reserved.
  • Periocular injection of in situ hydrogels containing Leu-Ile, an inducer for neurotrophic factors, promotes retinal ganglion cell survival after optic nerve injury, Masayoshi Nakatani, Yuko Shinohara, Miki Takii, Hisato Mori, Nobuharu Asai, Shigeru Nishimura, Yoko Furukawa-Hibi, Yoshiaki Miyamoto, Atsumi Nitta, EXPERIMENTAL EYE RESEARCH, 93, (6) 873 - 879,   2011年12月, 査読有り, Intraocular administration of neurotrophic factors has been shown to delay irreversible degeneration of retinal ganglion cells (RGCs). It would be beneficial for the treatment of optic nerve (ON) injury if such neurotrophic factors could be delivered in a less-invasive manner. The dipeptide leucine-isoleucine (Leu-Ile) appears to induce the production of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), in the brain. We therefore administered Leu-Ile via periocular depot injection in rats and investigated the dipeptide's ability to induce BDNF and GDNF in the retina and to delay RGC loss in an ON injury model. Poloxamer-alginate hydrogels containing Leu-Ile were injected into the subconjunctival space of intact or ON-injured rats. BDNF and GDNF levels in the retina were determined by an enzyme immunoassay. Survival of RGCs was assessed in retinal flatmounts. Activation of extracellular signal-regulated kinases (ERR) and cAMP response element binding protein (CREB) in the retina was examined by Western blotting. At 2 h after injection of fluorescein isothiocyanate-conjugated Leu-Ile, the fluorescence intensities in the retina were 4.3-fold higher than those in the saline control. Treatment with Leu-Ile significantly increased the retinal levels of BDNF at 6 h and GDNF at 6-72 h after injection. Treatment with Leu-Ile significantly increased RGC survival to 14 days after ON injury and enhanced the activation of ERK at 72 h and CREB at 48 h after injection in the ON-injured retina. These results suggest that periocular delivery of Leu-Ile induces BDNF and GDNF production in the retina, which may eventually enhance RGC survival after ON injury. (C) 2011 Elsevier Ltd. All rights reserved.
  • Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice., Furukawa-Hibi, Y, Alkam T, Nitta, A, Matsuyama, A, Mizoguchi, H, Suzuki, K, Moussaoui, S, Yu, Q-S, Greig, N, Nagai, T, Yamada, K, Behavioural Brain Research, 225, (1) 222 - 229,   2011年11月, 査読有り
  • The hydrophobic dipeptide Leu-Ile inhibits immobility induced by repeated forced swimming via the induction of BDNF, Yoko Furukawa-Hibi, Atsumi Nitta, Takeshi Ikeda, Koji Morishita, Wenting Liu, Daisuke Ibi, Tursun Alkam, Toshitaka Nabeshima, Kiyofumi Yamada, BEHAVIOURAL BRAIN RESEARCH, 220, (2) 271 - 280,   2011年07月, 査読有り, Depression has recently become a serious. problem in society worldwide. However, we lack appropriate therapeutic tools, since the causes of depression remain unclear. Degeneration of neuronal cells and a decrease in neurogenesis have been suggested recently as two of the factors responsible for depression-like behavior. Furthermore, brain-derived neurotrophic factor (BDNF) is also suggested to be an important factor in recovering from such behavior. We have previously demonstrated that the hydrophobic dipeptide leucyl-isoleucine (Leu-Ile) induces BDNF in cultured neuronal cells. We therefore investigated possible antidepressant-like effects of Leu-Ile in an animal model using the repeated forced swim test (FST). Mice were forced to swim for 6 min once a day in a cylinder containing water. The mice were treated with Leu-Ile s.c. or p.o. immediately after each FST. Five-day repeated Leu-Ile treatment significantly increased BDNF mRNA levels and activated the BDNF/Akt/mTOR signaling pathway in the hippocampi of the mice. While 2-week repeated FST increased immobility time, Leu-Ile treatment for 2 weeks offset this increase. In C57BL/6J-BDNF heterozygous knockout (BDNF(+/-)) mice, Leu-Ile failed to reduce the immobility time increased by repeated FST. We next investigated the extent of cell proliferation in the hippocampus as 5-bromo-2'-deoxy-uridine (BrdU) uptake into hippocampal cells. Repeated FST significantly reduced the number of BrdU-positive cells in the hippocampal dentate gyrus, while this deficit was prevented by repeated Leu-Ile treatment. These results suggest that Leu-Ile has an antidepressant-like effect, at least in part by supporting cell proliferation through the BDNF signaling pathway. (C) 2011 Elsevier B.V. All rights reserved.
  • Overexpression of piccolo C2A domain induces depression-like behavior in mice, Yoko Furukawa-Hibi, Atsumi Nitta, Hidefumi Fukumitsu, Hitomi Somiya, Shoei Furukawa, Toshitaka Nabeshima, Kiyofumi Yamada, NEUROREPORT, 21, (18) 1177 - 1181,   2010年12月, 査読有り, Piccolo is one of the components of the active zone at chemical synapses and regulates the transport of synaptic vesicles. The piccolo C2A domain is an important calcium sensor and binds with phosphatidylinositol or synaptotagmin-1. Recently, clinical studies suggested that a single nucleotide polymorphism in the piccolo C2A domain might be a causal risk factor for major depression. To clarify the association of piccolo with depression, we produced a transgenic mouse overexpressing the C2A domain of piccolo, and investigated the behavior of these mice. The mice exhibited depression-like behavior in both forced swim and tail suspension tests, suggesting that piccolo might regulate the depressive behavior. NeuroReport 21: 1177-1181 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
  • [Identification of Piccolo as a regulator of behavioral plasticity and dopamine transporter internalization]., Nitta A, Hibi Y, Miyamoto Y, Nabeshima T, Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence, 45, (6) 525 - 529,   2010年12月, 査読有り
  • Oral supplementation with Leu-Ile, a hydrophobic dipeptide, prevents the impairment of memory induced by amyloid beta in mice via restraining the hyperphosphorylation of extracellular signal-regulated kinase, Tursun Alkam, Atsumi Nitta, Yoko Furukawa-Hibi, Minae Niwa, Hiroyuku Mizoguchi, Kiyofumi Yamada, Toshitaka Nabeshima, BEHAVIOURAL BRAIN RESEARCH, 210, (2) 184 - 190,   2010年07月, 査読有り, 招待有り, Restraining the toxic pathways of amyloid beta peptide (A beta) by daily supplementation with dietary products has been shown effective in preventing cognitive decline. In this study, we examined the effects of the orally administered Leu-Ile, a hydrophobic dipeptide, on the neurotoxicity of A beta(25-35) in mice. Chronic daily treatment with Leu-Ile prevented the A beta(25-35)-induced protein nitration and impairment of novel object recognition memory in mice. Protein nitration in the hippocampus induced by A beta(25-35) was associated with the hyperphosphorylation of extracellular signal-regulated kinase (ERK) which was found responsible for the over-expression of inducible nitric oxide synthase. Sub-chronic treatment with Leu-Ile prevented the A beta(25-35)-induced hyperphosphorylation of ERK and protein nitration in the hippocampus. The results suggested that with the protective property against the neurotoxicity of A beta(25-35), Leu-Ile could be considered as a candidate for the dietary supplementation in the prevention of A beta-related impairment of recognition memory. (C) 2010 Elsevier B.V. All rights reserved.
  • [Possible relation of BDNF and GDNF to neuropsychiatric disorders]., Hibi Y, Nitta A, Nabeshima T, Yamada K, Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology, 29, (2) 85 - 89,   2009年04月, 査読有り
  • SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress, Y Kobayashi, Y Furukawa-Hibi, C Chen, Y Horio, K Isobe, K Ikeda, N Motoyama, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 16, (2) 237 - 243,   2005年08月, 査読有り, Forkhead transcription factor, DAF-16, regulates genes that contribute both to longevity and resistance to various stresses in C elegans. We and others have reported that members of the FOXO, mammalian homologs of DAF- 16, also regulate genes related to stress resistance, such as GADD45. The NAD-dependent protein deacetylase, SIR2, is required for life span extension in yeast induced by caloric restriction, which also increases longevity in a wide variety of other organisms, including mammals. Sir2. 1, a homolog of yeast SIR2, also extends life span by acting in a DAF-16 signaling pathway in C. elegans. We demonstrate that mammalian SIRT1 (Sir2 alpha) physiologically interacts with FOXO. Acetylation of FOXO4, by the transcriptional coactivator p300, counteracted transcriptional activation of FOXO4 by p300. In contrast, mammalian SIRT1 was found to bind to FOXO4, catalyze its deacetylation in an NAD-dependent manner, and thereby increase its transactivation activity. The activity of FOXO4 is suppressed or enhanced by SIRT1 inhibitor, nicotinamide, or its activator, resveratrol, respectively. In response to oxidative stress, FOXO accumulates within the nucleus and induces GADD45 expression. FOXO-mediated GADD45 induction is markedly impaired in the cell, which depleted SIRT1 expression by RNA-interference. These results indicate that mammalian SIRT1 plays a pivotal role for FOXO function via NAD-dependent deacetylation in response to oxidative stress, and thereby may contribute to cellular stress resistance and longevity.
  • SIRT1 is critical regulator for FOXO-mediated gene transcription in response to oxidative stress, Kobayashi, Y, Furukawa-Hibi, Y, Chen, C, Horio, Y, Isobe, K, Ikeda, K, Motoyama, N, J. Mol. Med., 16,   2005年, 査読有り
  • FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress, Y Furukawa-Hibi, K Yoshida-Araki, T Ohta, K Ikeda, N Motoyama, JOURNAL OF BIOLOGICAL CHEMISTRY, 277, (30) 26729 - 26732,   2002年07月, 査読有り, Members of the FOXO family of mammalian forkhead transcription factors, including AFX, FKHRL1, and FKHR, are homologs of DAF-16, which regulates genes that contribute both to longevity and to resistance to various stresses (including oxidative stress) in Caenorhabditis elegans. We have generated mouse myoblastic C2C12 cell lines in which expression of a constitutively active form of AFX (AFX-TM) is inducible by Cre-mediated recombination at loxP sites. Here we show that forced expression of AFX-TM blocked cell cycle progression at the G(1) and G(2) phases and that FOXO family members regulated the expression of stress-inducible genes such as GADD45. AFX and FKHRL1 each directly activated the GADD45 promoter through interaction with FOXO binding motifs. Oxidative stress activated the GADD45 promoter in a FOXO-dependent manner, resulting in an increased abundance of GADD45 mRNA and protein as well as G(2) arrest. These responses were evident in cells in which the tumor suppressor protein p53 was inactivated. Our results suggest that the FOXO family of transcription factors plays an important role in the regulation of GADD45 in response to oxidative stress and thereby contributes to G(2)-M checkpoint.
  • Calcium signals in rat bashophilic leukemia (RBL-2H3) cells primed with the neuropeptide substance P., Furukawa, Y, Furuno, T, Teshima, R, Nakanishi, M, Biol. Pharm. Bull., 24, (9) 1060 - 1063,   2001年, 査読有り
  • Mutational analysis of the C-terminal signal peptide of bovine liver 5'-nucleotidase for GPI-anchoring. A study on significance of the hydrophilic spacer region., Furukawa, Y, Tsukamoto, K, Ikezawa, H, Biochim. Biophys. Acta, 1328,   1997年, 査読有り
  • Mutational analysis of the COOH-terminal hydrophobic domain of bovine liver 5'-nucleotidase as a signal for glycosylphosphatidylinositol (GPI) anchor attachment., Furukawa, Y, Tamura, H, Ikezawa, H, Biochim. Biophys. Acta, 1190, (2) 273 - 278,   1994年, 査読有り
  • Purification and cDNA cloning of bovine liver 5'-nucleotidase, a GPI-anchored protein, and its expression in COS cells., Suzuki, K, Furukawa, Y, Tamura, H, Ejiri, N, Suematsu, H, Taguchi, R, Nakamura, S, Suzuki, Y, Ikezawa, H, J. Biochem., 113,   1993年, 査読有り

MISC

  • アルツハイマー型認知症治療薬について, 日比陽子, ファルマシア, 49,   2013年, 招待有り
  • 神経系におけるブチリルコリンエステラーゼの機能, 日比陽子, 山田清文, Clinical Neuroscience, 30,   2012年, 招待有り
  • ストレスにより誘発される脳機能障害とストレス応答性転写因子Npas4の機能解析, 永井 拓, 尹 在錫, 衣斐大祐, 小池宏幸, 日比陽子, 山田清文, 日本薬理学雑誌, 139,   2012年
  • DNAメチル化と正常大腸 -特にfield cancerizationについて-, 前田 修, 安藤貴文, 石黒和博, 渡辺 修, 日比陽子, 永井 拓, 山田清文, 舩坂好平, 宮原良二, 大宮直木, 後藤秀実, Jean-Pierre J.Issa, 生物物理化学, 56,   2012年
  • ストレスによる精神疾患の発症にDNAメチル化が関与する, 日比陽子, ファルマシア, 47,   2011年07月01日, 招待有り
  • 名古屋大学医学部附属病院における6年制実務実習の特色, 日比陽子, 葛谷孝文, 重野克郎, 椿井 朋, 野田幸裕, 山田清文, 愛知県病院薬剤師会雑誌, 39,   2011年, 招待有り
  • 第2回認定実務実習指導者連絡会報告, 日比 陽子, 愛知県病院薬剤師会雑誌, 39,   2011年
  • 薬物依存におけるピッコロの役割, 新田淳美, 日比陽子, 宮本嘉明, 鍋島俊隆, 日本アルコール・薬物医学会雑誌, 45,   2010年
  • 脳由来神経栄養因子およびグリア細胞由来神経栄養因子と神経精神疾患との関係., 日比陽子, 新田淳美, 鍋島俊隆, 山田清文, 日本神経精神薬理学雑誌, 29,   2009年, 招待有り
  • 11th CongressoftheInternationalAssociation ofBiomedicalGerontology(IABG)参加記, 日比 陽子, 基礎老化研究, 29,   2005年, 招待有り
  • 酸化ストレスによるフォークヘッド型転写因子FOXOファミリーの活性制御, 日比(古川)陽子, 小林 洋介, 本山 昇, 基礎老化研究, 29,   2005年, 招待有り
  • FOXO Transcription factors in cell cycle regulation and the response to oxidative stress., Furukawa-Hibi Y, Kobayashi Y, Chen C, Motoyama N, Antioxid. Redox Signal., 7,   2005年, 招待有り

書籍等出版物

  • 薬学生のための病院実務実習ワークブック 第2版, 共著, 分担執筆, 第4章 病棟実習(薬物血中濃度モニタリング(TDM)実習), じほう,   2013年03月

講演・口頭発表等

  • 名古屋大学医学部附属病院の新コアカリキュラム実務実習に向けた調査 ~主に「代表的な8疾患」の経験について~, 日比陽子, 伊藤教道, 梅村 朋, 堀場崇志, 白松貴子, 吉見 陽, 野田幸裕, 山田清文, 日本薬学会第138年会,   2018年03月25日
  • 名古屋大学医学部附属病院における実務実習の現状 ~新コアカリキュラム実習に向けて~, 日比陽子, 伊藤教道, 椿井 朋, 白松貴子, 吉見 陽, 野田幸裕, 山田清文, 医療薬学フォーラム2017,   2017年07月01日
  • 脳神経疾患に対するジペプチドLeu-Ileの効果について, 日比陽子, アルカム トルソン, 鍋島俊隆, 新田淳美, 第18回応用薬理シンポジウム,   2016年08月05日
  • 名古屋大学医学部附属病院における実務実習, 日比陽子, 伊藤教道, 矢野亨治, 野田幸裕, 毛利彰宏, 椿井 朋, 西川佐紀子, 山田清文, 医療薬学フォーラム2015/第23回クリニカルファーマシーシンポジウム,   2015年07月04日
  • メマンチンはアミロイドβ誘発性認知機能障害を改善する, 日比陽子, 山田清文, 第24回日本医療薬学会年会,   2014年09月27日
  • 名古屋大学医学部附属病院における実務実習スケジュール改訂, 日比陽子, 矢野亨治, 椿井 朋, 西川佐紀子, 野田幸裕, 毛利彰宏, 山田清文, 日本薬学会第134年会,   2014年03月28日
  • 長期ストレスはGABA神経関連転写因子Npas4遺伝子のDNAメチル化を亢進する, 日比(古川) 陽子, 永井 拓, 山田 清文, 第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会合同年会,   2013年10月24日
  • 脳特異的転写因子Npas4欠損マウスにおける異常行動とGABA作動性神経系マーカーの変化, 日比(古川) 陽子, 横井 順平, 永井 拓, 山田 清文, 第123回日本薬理学会近畿部会,   2013年07月12日
  • Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via glucocorticoid receptor in the brain, Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, 11th WFSBP,   2013年06月23日
  • グルココルチコイド受容体は神経分化関連因子NPAS4の転写を直接抑制する, Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, 第86回日本薬理学会,   2013年03月21日
  • Glucocorticoid reduces the gene expression of neuronal PAS domain 4 (Npas4) in the brain., Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, ASCB2012,   2012年12月15日
  • Stress regulates the gene expression of neuronal transcription factor Npas4 via glucocorticoid, Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, 第4回GCOE国際シンポジウム,   2012年11月15日
  • Transcriptional regulation of neuronal PAS domain 4 (NPAS4) by glucocorticoid receptor, Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, The 11th APSN The 55th JSN,   2012年09月30日
  • Stress regulates the gene expression of neuronal PAS domain 4 (Npas4), via glucocorticoid receptor., Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, CINP2012,   2012年06月03日
  • 名古屋大学医学部附属病院における薬学部学生の長期実務実習カリキュラムの見直し, 日比陽子, 葛谷孝文, 重野克郎, 椿井 朋, 野田幸裕, 山田清文, 日本薬学会第132年会,   2012年03月28日
  • グルココルチコイドによる転写因子NPAS4の発現抑制機構, 日比 陽子, ユン ジェスク, 永井 拓, 山田 清文, 第7回統合失調症学会,   2012年03月16日
  • ブチリルコリンエステラーゼ阻害剤のアミロイドベータ誘発性認知機能障害改善効果, 日比(古川)陽子, アルカム・トルソン, 新田淳美, 松山明裕, 永井拓, 山田清文, 第85回日本薬理学会年会,   2012年03月14日
  • 神経発達関連転写因子NPAS4の発現調節機構の解明, 日比(古川)陽子, ユン ジェスク, 永井 拓, 山田 清文, 第34回日本分子生物学会年会,   2011年12月13日
  • 名古屋大学医学部附属病院における実務実習初年度の成果と平成23年度の新たな試み, 日比陽子, 葛谷孝文, 重野克郎, 椿井 朋, 野田幸裕, 山田清文, 第21回日本医療薬学会年会,   2011年10月01日
  • OVER EXPRESSION OF PICCOLO C2A DOMAIN INDUCES DEPRESSION-LIKE BEHAVIOR IN MICE, Atsumi Nitta, Yoko Furukawa-Hibi, Toshitaka Nabeshima, AsCNP2011,   2011年09月23日
  • Overexpressions of, shati, in the dorsal striatum or nucleus accumbens affect emotional behaviors in mice, Noriyuki Iegaki, Yoshiaki Miyamoto, Yudai Ishikawa, Yoko Furukawa-Hibi, Shin-ichi Muramatsu, Toshitaka Nabeshima, Atsumi Nitta, AsCNP2011,   2011年09月23日
  • Role of a novel molecule ,shati, in animal model of dystonia, Eriko Saika, Yoshiaki Miyamoto, Yoko Furukawa-Hibi, Shin-ichi Muramatsu, Toshitaka Nabeshima, Atsumi Nitta, AsCNP2011,   2011年09月23日
  • The Role of Npas4 in Neurite Outgrowth and phosphorylation of Synapsin I, Jaesuk Yun, Taku Nagai, Yoko Hibi, Keisuke Kuroda, Kozo Kaibuchi, Kiyofumi Yamada, AsCNP2011,   2011年09月23日
  • Stress reduces the expression of transcription factor, neuronal PAS domain 4 (NPAS4)., Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, AsCNP,   2011年09月23日
  • ストレスによるneuronal PAS domain 4 (NPAS4)の転写制御, Yoko Hibi, Jaesuk Yun, Taku Nagai, Kiyofumi Yamada, Neuroscience 2011,   2011年09月14日
  • 神経発達関連転写因子NPAS4のストレスによる転写抑制機構の解明, 日比(古川)陽子, ユン ジェスク, 永井 拓, 山田 清文, 第119回日本薬理学会近畿部会,   2011年07月08日
  • ストレスによる脳特異的転写因子NPAS4の転写抑制機構の解明, 日比(古川)陽子, Yun Jaesk, 永井拓, 山田清文, 第84回日本薬理学会年会,   2011年03月22日
  • Stress regulates the expression of neuronal PAS domain 4 (NPAS4), Yoko Hibi, Jaesk Yun, Taku Nagai, Kiyofumi Yamada, GCOEグローバルリトリート,   2011年02月25日
  • ストレスによる脳特異的転写因子NPAS4の転写抑制機構の解析, 日比-古川 陽子, Yun Jaesk, 永井 拓, 山田 清文, BMB2010(第33回日本分子生物学会年会、第83回日本生化学会合同年会),   2010年12月07日
  • 名古屋大学付属病院における6年制実務実習の特色~利点と問題点~, 日比陽子, 葛谷孝文, 重野克郎, 椿井 朋, 野田幸裕, 山田清文, 日本薬学会東海支部会,   2010年11月28日
  • 脳特異的転写因子NPAS4はストレスにより転写抑制される, 日比(古川)陽子, Jaesk Yun, 永井拓, 山田清文, 第118回日本薬理学会近畿部会,   2010年11月19日
  • 名古屋大学医学部附属病院における6年制実務実習, 日比陽子, 葛谷孝文, 重野克郎, 椿井 朋, 野田幸裕, 山田清文, 第20回日本医療薬学会年会,   2010年11月13日
  • Neuronal PAS domain 4 (NPAS4)のストレスによる転写制御機構の解明, 日比陽子, Yun Jaesk, 早川浩史, 永井拓, 山田清文, GCOE第3回国内シンポジウム,   2010年11月05日
  • ブチリルコリンエステラーゼ阻害剤はアミロイドベータにより誘発される認知機能障害を改善する, 日比(古川)陽子, アルカム トルソン, 新田淳美, 松山明裕, Nigel H. Greig, 永井拓, 山田清文, 第20回日本臨床精神神経薬理学会第40回日本神経精神薬理学会 合同年会,   2010年09月15日
  • アミロイドベータにより誘導されるチロシンニトロ化に対するアセチルコリンエステラーゼ阻害剤の効果, 日比(古川)陽子, アルカム・トルソン, 新田淳美, 松山明裕, 永井拓, 山田清文, 第33回日本基礎老化学会,   2010年06月18日
  • Dipeptide Leu-Ile inhibits immobility induced by repeated forced swimming via induction of BDNF., Furukawa-Hibi, Y, Nitta, A, Ikeda, T, Morishita, K, Nabeshima, T, Yamada, K, The 6th Nagoya / Nanjing / Shenyang Symposium of Pharmaceutical Sciences,   2009年09月14日
  • Oxidative stress induces the FOXO activation by dephosphorylation., Furukawa-Hibi, Y, Ito, Y, Matsumoto, M, Iemura, S.-I, Natsume, T, Watanabe, K, Nitta, A, Motoyama, N, 37th Annual Meeting of Society for Neuroscience,   2007年11月03日
  • Nuclear Accumulation of FOXO in Response to Oxidative Stress Is Regulated by Protein Phosphatase 2A., Yoko Furukawa-Hibi, Shun-ichiro Iemura, Tohru Natsume, Ken Watanabe, Noboru Motoyama, 2006 Gordon Research Conference, Aging, Biology Of,   2006年
  • Oxidative stress activates the forkhead transcription factor, FOXO family, Yoko Furukawa-Hibi, Yosuke Kobayashi, Kyoji Ikeda, Noboru Motoyama, 2004 Spring Conference of the Korean Society for Gerontology and the 4th Korea-Japan Gerontologist Joint Meeting,   2004年
  • Forkhead transcription factors activate the stress-inducible gene GADD45 in response to oxidative stress, Yoko Furukawa-Hibi, Kiyomi Yoshida-Araki, Tsutomu Ohta, Kyoji Ikeda, Noboru Motoyama, Cold Spring Harbor Laboratory Molecular Genetics of Aging meeting (CSHL),   2002年
  • Mutational analysis of the C-terminal Signal peptide of bovine liver 5'-nucleotidase for the GPI-anchoring, Yoko Furukawa, Kikuo Tsukamoto, Hiroh Ikezawa, 37th International Conference on the Biochemistry of Lipids (ICBL),   1996年

特許

  • 眼科用薬剤, 中谷正義, 篠原結子, 平林美紀, 鈴森千智, 西村茂, 新田淳美, 日比陽子, 特願2008-206491, 特許5340667

競争的資金

  • ストレス感受性転写因子NPAS4を標的とした神経精神疾患治療薬の開発, 日本学術振興会, 科学研究費助成事業,   2017年04月 - 2020年03月
  • ストレス感受性転写因子NPAS4の機能破綻による精神疾患発症機構の解析, 日本学術振興会, 科学研究費助成事業,   2014年04月 - 2018年03月
  • ストレスによる精神疾患発症における脳特異的転写因子NPAS4の役割, 日本学術振興会, 科学研究費助成事業,   2011年04月 - 2014年03月
  • 新規薬物依存タンパクshatiの生理機能解析, 日本学術振興会, 科学研究費助成事業,   2009年04月 - 2010年03月
  • 神経・精神疾患に関与する新規分子の機能解明および臨床応用への可能性, 日本学術振興会, 科学研究費助成事業,   2009年04月 - 2010年03月
  • 認知機能障害モデルマウスを用いた治療薬の開発とその作用機序の解明, 科学研究費助成事業,   2009年04月 - 2010年03月, アミロイドベータを脳室内投与したモデルマウスに新規物体認知試験を行うと、認知記憶の低下が認められる。このモデルを用い、認知機能改善薬の薬効解析を行った。アミロイドベータの投与は海馬蛋白質のニトロ化など酸化ストレスを引き起こすが、認知機能改善薬の数日投与により、この海馬蛋白質ニトロ化が抑制された。
  • フォークヘッド型転写因子FOXOの機能解析, 日本学術振興会, 科学研究費助成事業,   2004年01月 - 2005年10月, 細胞分化や細胞保護作用を示すFOXOファミリー転写因子が酸化ストレスにより脱リン酸化されて核局在し、脱アセチル化酵素SIRT1で脱リン酸化され活性化することを明らかにした。


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