Study on the molecular mechanism of psychiatric disorders that targets PACAP signaling pathways and aimed at the development of therapeutic drug
Project/Area Number |
26293020
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Pharmacology in pharmacy
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
早田 敦子 大阪大学, 連合小児発達学研究科, 助教 (70390812)
|
Co-Investigator(Renkei-kenkyūsha) |
HASHIMOTO Ryota 大阪大学, 大学院連合小児発達学研究科, 准教授 (10370983)
|
Project Period (FY) |
2014-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
Keywords | PACAP / 精神疾患 / 創薬 / 薬学 / 国際情報交換 |
Outline of Final Research Achievements |
Pathophysiological mechanisms for psychiatric disorders remain poorly understood, which need to be urgently addressed. Recent studies have suggested that PACAP is implicated in neuropsychological functions and the risk and pathogenesis of psychiatric disorders. In this study, in order to obtain insights relevant to drug development, we examined brain signaling pathways as well as intracellular signaling pathways that are relevant to PACAP-dependent signaling. We obtained the data showing that the implication of noradrenaline in PACAP-deficient mouse phenotypes, involvement of BDNF signaling in PACAP-dependent axon outgrowth, necessity of β-arrestin2 for PACAP-induced 5-HT2A receptor internalization, and interaction and internalization of PACAP receptor PAC1 with β-arrestin2, which induces prolonged ERK1/2 activation. The present observations as well as the assay systems generated are expected to contribute to future drug discovery research.
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Report
(5 results)
Research Products
(133 results)
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[Journal Article] Targeted knockdown of the mitochondria-localized protein p13 protects against experimental parkinsonism2018
Author(s)
Inoue N, Ogura S, Kasai A, Nakazawa T, Ikeda K, Higashi S, Isotani A, Baba K, Mochizuki H, Fujimura H, Ago Y, Hayata-Takano A, Seiriki K, Shintani N, Hashimoto H
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Journal Title
EMBO Reports
Volume: 19(3)
Pages: e44860
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Peer Reviewed / Open Access
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[Journal Article] Unbiased compound screening with a reporter gene assay highlights the role of p13 in the cardiac cellular stress response2018
Author(s)
Inoue N, Hirouchi T, Kasai A, Higashi S, Hiraki N, Tanaka S, Nakazawa T, Nunomura K, Lin B, Omori A, Hayata-Takano A, Kim YJ, Doi T, Baba A, Hashimoto H, Shintani N
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 495(2)
Pages: 1992-1997
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[Journal Article] Disturbed spermatogenic signaling in pituitary adenylate cyclase activating polypeptide-deficient mice2018
Author(s)
Reglodi D, Cseh S, Somoskoi B, Fulop BD, Szentleleky E, Szegeczki V, Kovacs A, Varga A, Kiss P, Hashimoto H, Tamas A, Bardosi A, Manavalan S, Bako E, Zakany R, Juhasz T
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Journal Title
Reproduction
Volume: 155(2)
Pages: 129-139
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background2018
Author(s)
Farkas J, Kovacs LA, Gaspar L, Nafz A, Gaszner T, Ujvari B, Kormos V, Csernus V, Hashimoto H, Reglodi D, Gaszner B
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Journal Title
Neuroscience
Volume: 354
Pages: 11-29
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[Journal Article] Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice2017
Author(s)
Hara Y, Ago Y, Taruta A, Hasebe S, Kawase H, Tanabe W, Tsukada S, Nakazawa T, Hashimoto H, Matsuda T, Takuma K
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Journal Title
Psychopharmacology (Berl)
Volume: 234(21)
Pages: 3217-3228
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Peer Reviewed
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[Journal Article] High-speed and scalable whole-brain imaging in rodents and primates2017
Author(s)
Seiriki K, Kasai A, Hashimoto T, Schulze W, Niu M, Yamaguchi S, Nakazawa T, Inoue K, Uezono S, Takada M, Naka Y, Igarashi H, Tanuma M, Waschek JA, Ago Y, Tanaka KF, Hayata-Takano A, Nagayasu K, Shintani N, Hashimoto R, Kunii Y, Hino M, Matsumoto J, Yabe H, Nagai T, Fujita K, Matsuda T, Takuma K, Baba A, Hashimoto H
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Journal Title
Neuron
Volume: 94
Pages: 1085-1100
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[Journal Article] Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior2017
Author(s)
Fujita Y, Masuda K, Bando M, Nakato R, Katou Y, Tanaka T, Nakayama M, Takao K, Miyakawa T, Tanaka T, Ago Y, Hashimoto H, Shirahige K, Yamashita T
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Journal Title
J. Exp. Med.
Volume: 214
Pages: 1431-1452
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Peer Reviewed
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[Journal Article] Effct of clozapine on DNA methylation in peripheral leukocytes from patients with treatment-resistant schizophrenia2017
Author(s)
Kinoshita M, Numata S, Tajima A, Yamamori H, Yasuda Y, Fujimoto M, Watanabe S, Umehara H, Shimodera S, Nakazawa T, Kikuchi M, Nakaya A, Hashimoto H, Imoto I, Hashimoto R, Ohmori T
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Journal Title
Int. J. Mol. Sci.
Volume: 18
Pages: E632
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Peer Reviewed / Open Access
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[Journal Article] Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine2017
Author(s)
Nakazawa T, Kikuchi M, Ishikawa M, Yamamori H, Nagayasu K, Matsumoto T, Fujimoto M, Yasuda Y, Fujiwara M, Okada S, Matumura K, Kasai A, Hayata-Takano A, Shintani N, Numata S, Takuma K, Akamatsu W, Okano H, Nakaya A, Hashimoto H, Hashimoto R
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Journal Title
Schizophr. Res.
Volume: 181
Pages: 75-82
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Peer Reviewed
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[Journal Article] Implantable optogenetic device with CMOS IC technology for simultaneous optical measurement and stimulation2017
Author(s)
Haruta M, Kamiyama N, Nakajima S, Motoyama M, Kawahara M, Ohta Y, Yamasaki A, Takehara H, Noda T、Sasagawa K, Ishikawa Y, Tokuda T, Hashimoto H, Ohta J
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Journal Title
Japanese J. Appl. Physics
Volume: 56
Pages: 057001
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[Journal Article] Decreased cohesion in the brain leads to defective synapse development and anxiety-related behavior2017
Author(s)
Fujita Y, Masuda K, Bando M, Nakato R, Katou Y, Tanaka T, Nakayama M, Takao K, Miyakawa T, Tanaka T, Ago Y, Hashimoto H, Shirahige K, Yamashita T.
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Journal Title
J. Exp. Med.
Volume: 印刷中
Pages: 印刷中
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Peer Reviewed
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[Journal Article] Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia2017
Author(s)
Kinoshita M, Numata S, Tajima A, Yamamori H, Yasuda Y, Fujimoto M, Watanabe S, Umehara H, Shimodera S, Nakazawa T, Kikuchi M, Nakaya A, Hashimoto H, Imoto I, Hashimoto R, Ohmori T.
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Journal Title
Int. J. Mol. Sci.
Volume: 18(3)
Pages: 632
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[Journal Article] Prostaglandin D2 signaling mediated by the CRTH2 receptor is involved in MK-801-induced cognitive dysfunction2016
Author(s)
Onaka Y, Shintani N, Nakazawa T, Kanoh T, Ago Y, Matsuda T, Hashimoto R, Ohi K, Hirai H, Nagata KY, Nakamura M, Kasai A, Hayata-Takano A, Nagayasu K, Takuma K, Ogawa A, Baba A, Hashimoto H.
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Journal Title
Behav. Brain. Res.
Volume: 314
Pages: 77-86
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Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers2016
Author(s)
Kormos V, Gaspar L, Kovacs, Farkas J, Gaszner T, Csernus V, Balogh A, Hashimoto H, Reglodi D, Helyes Z, Gaszner B.
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Journal Title
Neuroscience
Volume: 330
Pages: 335-358
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Peer Reviewed / Int'l Joint Research
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[Journal Article] PACAP suppresses dry eye signs by stimulating tear secretion2016
Author(s)
Nakamachi T, Ohtaki H, Seki T, Yofu S, Kagami N, Hashimoto H, Shintani N, Baba A, Mark L, Lanekoff I, Kiss P, Farkas J, Reglodi D, Shioda S.
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Journal Title
Nat. Commun.
Volume: 7
Pages: 12034
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Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] De novo POGZ mutations in sporadic autism disrupt the DNA-binding activity of POGZ2016
Author(s)
Matsumura K, Nakazawa T, Nagayasu K, Gotoda-Nishimura N, Kasai A, Hayata-Takano A, Shintani N, Yamamori H, Yasuda Y, Hashimoto R, Hashimoto H.
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Journal Title
J. Mol. Psychiatry
Volume: 4
Pages: 1
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Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder2016
Author(s)
Hashimoto R, Nakazawa T, Tsurusaki Y, Yasuda Y, Nagayasu K, Matsumura K, Kawashima H, Yamamori H, Fujimoto M, Ohi K, Umeda-Yano S, Fukunaga M, Fujino H, Kasai A, Hayata-Takano A, Shintani N, Takeda M, Matsumoto N, Hashimoto H.
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Journal Title
J Human Genet.
Volume: 61(3)
Pages: 199-206
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[Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in adult mouse hippocampal neurogenesis after stroke2016
Author(s)
Matsumoto M, Nakamachi T, Watanabe J, Sugiyama K, Ohtaki H, Murai N, Sasaki S, Xu Z, Hashimoto H, Seki T, Miyazaki A, Shioda S.
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Journal Title
J Mol Neurosci.
Volume: 未定
Pages: 未定
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Peer Reviewed
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[Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor2016
Author(s)
Xu Z, Ohtaki H, Watanabe J, Miyamoto K, Murai N, Sasaki S, Matsumoto M, Hashimoto H, Hiraizumi Y, Numazawa S, Shioda S.
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Journal Title
Sci Rep.
Volume: 6
Pages: 22373
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Peer Reviewed
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[Journal Article] Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders2016
Author(s)
Nakazawa T, Hashimoto R, Sakoori K, Sugaya Y, Tanimura A, Hashimotodani Y, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Yokoyama K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M.
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Journal Title
Nat Commun.
Volume: 7
Pages: 10594
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[Journal Article] Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)2015
Author(s)
Shibasaki Y, Hayata-Takano A, Hazama K, Nakazawa T, Shintani N, Kasai A, Nagayasu K, Hashimoto R, Tanida M, Katayama T, Matsuzaki S, Yamada K, Taniike M, Onaka Y, Ago Y, Waschek JA, Koves K, Reglodi D, Tamas A, Matsuda T, Baba A, Hashimoto H.
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Journal Title
Neuroscience
Volume: 297
Pages: 95-104
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Peer Reviewed / Int'l Joint Research
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[Journal Article] CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice2015
Author(s)
Onaka Y, Shintani N, Nakazawa T, Haba R, Ago Y, Wang H, Kanoh T, Hayata-Takano A, Hirai H, Nagata K, Nakamura N, Hashimoto R, Matsuda T, Waschek JA, Kasai A, Nagayasu K, Baba A, Hashimoto H.
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Journal Title
Behav Brain Res.
Volume: 284
Pages: 131-137
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.2015
Author(s)
Shibasaki Y, Hayata-Takano A, Hazama K, Nakazawa T, Shintani N, Kasai A, Nagayasu K, Hashimoto R, Tanida M, Katayama T, Matsuzaki S, Yamada K, Taniike M, Onaka Y, Ago Y, Waschek JA, Koves K, Reglodi D, Tamas A, Matsuda T, Baba A, Hashimoto H.
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Journal Title
Neuroscience
Volume: 297
Pages: 95-104
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Peer Reviewed / Acknowledgement Compliant
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[Journal Article] A mouse model of human primitive neuroectodermal tumors resulting from microenvironmentally-driven malignant transformation of orthotopically transplanted radial glial cells.2015
Author(s)
Malchenko S, Sredni ST, Hashimoto H, Kasai A, Nagayasu K, Xie J, Margaryan NV, Seiriki K, Lulla RR, Seftor RE, Pachman LM, Meltzer HY, Hendrix MJ, Soares MB.
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Journal Title
PLoS One
Volume: 10(3)
Pages: e0121707
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[Journal Article] PACAP Enhances Axon Outgrowth in Cultured Hippocampal Neurons to a Comparable Extent as BDNF.2015
Author(s)
Ogata K, Shintani N, Hayata-Takano A, Kamo T, Higashi S, Seiriki K, Momosaki H, Vaudry D, Vaudry H, Galas L, Kasai A, Nagayasu K, Nakazawa T, Hashimoto R, Ago Y, Matsuda T, Baba A, Hashimoto H.
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Journal Title
PLoS One
Volume: 10(3)
Pages: e0120526
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Simultaneous neuron- and astrocyte-specific fluorescent marking.2015
Author(s)
Schulze W, Hayata-Takano A, Kamo T, Nakazawa T, Nagayasu K, Kasai A, Seiriki K, Shintani N, Ago Y, Farfan C, Hashimoto R, Baba A, Hashimoto H.
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Journal Title
Biochem Biophys Res Commun.
Volume: 459(1)
Pages: 81-86
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice.2015
Author(s)
Onaka Y, Shintani N, Nakazawa T, Haba R, Ago Y, Wang H, Kanoh T, Hayata-Takano A, Hirai H, Nagata KY, Nakamura M, Hashimoto R, Matsuda T, Waschek JA, Kasai A, Nagayasu K, Baba A, Hashimoto H.
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Journal Title
Behav Brain Res.
Volume: 284
Pages: 131-137
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Identification of the role of bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro.2015
Author(s)
Yamasaki A, Kasai A, Toi A, Kurita M, Kimoto S, Hayata-Takano A, Nakazawa T, Nagayasu K, Shintani N, Hashimoto R, Ito A, Meltzer HY, Ago Y, Waschek JA, Onaka Y, Matsuda T, Baba A, Hashimoto H.
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Journal Title
J Neurochem.
Volume: 132(4)
Pages: 418-428
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Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Behavioral characterization of mice overexpressing human dysbindin-1.2014
Author(s)
Shintani N, Onaka Y, Hashimoto R, Takamura H, Nagata T, Umeda-Yano S, Mouri A, Mamiya T, Haba R, Matsuzaki S, Katayama T, Yamamori H, Nakazawa T, Nagayasu K, Ago Y, Yagasaki Y, Nabeshima T, Takeda M, Hashimoto H.
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Journal Title
Mol Brain.
Volume: 7(1)
Pages: 74
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Structural and morphometric comparison of the molar teeth in pre-eruptive developmental stage of PACAP-deficient and wild-type mice.2014
Author(s)
Sandor B, Fintor K, Felszeghy S, Juhasz T, Reglodi D, Mark L, Kiss P, Jungling A, Fulop BD, Nagy AD, Hashimoto H, Zakany R, Nagy A, Tamas A.
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Journal Title
J Mol Neurosci.
Volume: 54(3)
Pages: 331-341
DOI
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Peer Reviewed / Acknowledgement Compliant
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[Presentation] ASD-associated de novo mutations in POGZ impair the DNA-binding activity of POGZ2016
Author(s)
Nakazawa T, Matsumura K, Nagayasu K, Kasai A, Hayata-Takano A, Shintani N, Takuma K, Yamamori H, Yasuda Y, Hashimoto R, Hashimoto H.
Organizer
55th Annual Meeting, ACNP
Place of Presentation
アメリカ
Year and Date
2016-12-04 – 2016-12-08
Related Report
Int'l Joint Research
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[Presentation] 脳病態を解明するモデル動物の全脳イメージング2015
Author(s)
橋本均, 笠井淳司, 勢力薫, 丹生光咲, 中澤敬信
Organizer
第6回脳表現型の分子メカニズム研究会
Place of Presentation
コンベンションルームAP品川アネックスIルーム(東京・品川区)
Year and Date
2015-11-14 – 2015-11-15
Related Report
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[Presentation] Roles of PACAP in Depressopm-Like Behavior2015
Author(s)
Hashimoto H, Shintani N, Ago Y, Hayata-Takano A, Waschek JA, Baba A.
Organizer
12th International Symposium on VIP/PACAP and Related Peptides
Place of Presentation
カッパドキア(トルコ)
Year and Date
2015-09-21 – 2015-09-26
Related Report
Int'l Joint Research
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[Presentation] 自閉症の疾患特異的候補遺伝子の機能的スクリーニング2015
Author(s)
松村憲佑, 橋本亮太, 中澤敬信, 鶴崎美徳, 安田由華, 永安一樹, 川島和, 山森英長, 藤本美智子, 大井一高, 梅田知美, 福永雅喜, 藤野陽生, 笠井淳司, 早田敦子, 新谷紀人, 武田雅俊, 松本直通, 橋本均
Organizer
第38回日本神経科学大会
Place of Presentation
神戸国際会議場(兵庫・神戸市)
Year and Date
2015-07-28 – 2015-07-31
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[Presentation] がん治療後の脳機能障害の解明に有用な動物モデルの作製2015
Author(s)
尾中勇祐, 木野村元彦, 新谷紀人, 平井博之, 永田欽也, 中村正孝, 長谷部茂, 永安一樹, 吾郷由希夫, 笠井淳司, 早田敦子, 中澤敬信, 田熊一敞, 松田敏夫, 馬場明道, 橋本均
Organizer
第127回日本薬理学会近畿部会
Place of Presentation
長良川国際会議場(岐阜・岐阜市)
Year and Date
2015-06-26 – 2015-06-26
Related Report
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[Presentation] Brain-enriched Sorting Nexin Family Proteins Regulate Spine Morphogenesisand Are Associated with Risk for Schizophrenia2014
Author(s)
Nakazawa T, Hashimoto R, Tanimura A, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M
Organizer
ACNP 53rd Annual Meeting
Place of Presentation
Phoenix, AZ , USA
Year and Date
2014-12-07 – 2014-12-11
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[Presentation] 細胞内タンパク質輸送と統合失調症2014
Author(s)
中澤敬信、橋本亮太、橋本均
Organizer
生体機能と創薬シンポジウム2014
Place of Presentation
大阪 近畿大学薬学部 東大阪キャンパス
Year and Date
2014-08-28 – 2014-08-29
Related Report
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