Tsuyoshi Miyakawa Ph. D.

Professor

Fujita Health University

Location
Toyoake, Japan
Discipline
Biological Sciences
Interests
Biological basis of schizophrenia Dentate gyrus Relationships between genes and behavior
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About

I have been trying to find animal model of psychiatric disorders by using, what we call, a comprehensive behavioral tests battery on mutant mice. During these 17 years, I have looked at more nearly 140 strains of mutant mice, like knockout mice or transgenic mice. So far we have identified several different mice models of schizophrenia/bipolar disorders. Among them are forebrain calcineurin knockout mice and alpha-CaMKII HKO mice (Zeng et al., Cell, 2001; Miyakawa et al., PNAS, 2003; Gerber et al., PNAS, 2003; Yamasaki et al., Molecular Brain, 2008). We are also trying to find what's going on in the brains of those mice model of psychiatric disorders using a variety of techniques such as gene ship analysis, proteome analysis, neural activity mapping using c-Fos or Arc, electrophysiological analyses and etc.
Sar far, we have found a remarkable phenotype in the hippocampus of the brain, which I named, "immature Dentate Gyrus (=iDG)" (Yamasaki et al., Molecular Brain, 2008; Matsuo et al., Frontiers in Behavioral Neuroscience, 2009). In iDG of those animals, most of the DG neurons fail to mature and stay immature, even after the mice become adults.
We realized that this iDG phenotype is quite common among the mice showing hyperactivity and working memory deficit.
Interestingly, chronic treatment of Fluoxetine, a SSRI type of anti-depressants, can also cause iDG in normal B6 mice. We call it "dematuration" (Kobayashi et al, PNAS, 2010).
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Publications

  • T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

    Shoji H, Hagihara H, Takao K, Hattori S, Miyakawa T

    Journal of Visualized Experiments (2012)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Adenomatous polyposis coli heterozygous knockout mice display hypoactivity and age-dependent working memory deficits

    Koshimizu H, Takao K, Ohira K, Tanda K, Nakanishi K, Toyama K et al.

    Frontiers in Behavioral Neuroscience (2011)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • DIP/WISH deficiency enhances synaptic function and performance in the Barnes maze

    Asrar S, Kaneko K, Takao K, Negandhi J, Matsui M, Shibasaki K et al.

    Molecular Brain (2011)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

    Takeuchi H, Iba M, Inoue H, Higuchi M, Takao K, Tsukita K et al.

    PLoS ONE (2011)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory

    Kaitsuka T, Li S, Nakamura K, Takao K, Miyakawa T, Matsushita M

    Neurobiology of Learning and Memory (2011)

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  • Synaptic E3 Ligase SCRAPPER in Contextual Fear Conditioning: Extensive Behavioral Phenotyping of Scrapper Heterozygote and Overexpressing Mutant Mice

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • The Influence of Chronic Cerebral Hypoperfusion on Cognitive Function and Amyloid β Metabolism in APP Overexpressing Mice

    Yamada M, Ihara M, Okamoto Y, Maki T, Washida K, Kitamura A et al.

    PLoS ONE (2011)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice

    Ohira K, Miyakawa T

    Molecular Brain (2011)

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  • Relaxin-3-deficient mice showed slight alteration in anxiety-related behavior

    Tsujimura A, Nishi K, Yokoyama C, Miyakawa T, Tanaka M

    Frontiers in Behavioral Neuroscience (2011)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Expression of the AMPA Receptor Subunits GluR1 and GluR2 is Associated with Granule Cell Maturation in the Dentate Gyrus

    Hagihara H, Ohira K, Toyama K, Miyakawa T

    Frontiers in Neurogenesis (2011)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Behavioral profiles of three C57BL/6 substrains

    Matsuo N, Takao K, Nakanishi K, Yamasaki N, Tanda K, Miyakawa T

    Frontiers in Behavioral Neuroscience (2010)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Dissection of hippocampal dentate gyrus from adult mouse.

    Hagihara H, Toyama K, Yamasaki N, Miyakawa T

    Journal of visualized experiments JoVE (2009)

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  • Reversal of hippocampal neuronal maturation by serotonergic antidepressants

    Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T et al.

    Proceedings of the National Academy of Sciences of the United States of America (2010)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • SDOP-DB: A comparative standardised-protocol database for mouse phenotypic analyses

    Tanaka N, Waki K, Kaneda H, Suzuki T, Yamada I, Furuse T et al.

    Bioinformatics (Oxford, England) (2010)

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  • Comprehensive Behavioral Analysis of Calcium/Calmodulin-Dependent Protein Kinase IV Knockout Mice

    Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M et al.

    PLoS ONE (2010)

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  • Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells

    Ohira K, Furuta T, Hioki H, Nakamura K, Kuramoto E, Tanaka Y et al.

    Nat Neurosci (2009)

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  • Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice

    Matsuo N, Yamasaki N, Ohira K, Takao K, Toyama K, Eguchi M et al.

    Frontiers in Behavioral Neuroscience (2009)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Inhibition of calpain increases LIS1 expression and partially rescues in vivo phenotypes in a mouse model of lissencephaly

    Yamada M, Yoshida Y, Mori D, Takitoh T, Kengaku M, Umeshima H et al.

    Nat Med (2009)

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  • Mice with Altered Myelin Proteolipid Protein Gene Expression Display Cognitive Deficits Accompanied by Abnormal Neuron-Glia Interactions and Decreased Conduction Velocities

    Tanaka H, Ma J, Tanaka K, Takao K, Komada M, Tanda K et al.

    J. Neurosci. (2009)

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  • Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders

    Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M et al.

    Molecular Brain (2008)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Comprehensive behavioral phenotyping of calpastatin-knockout mice

    Nakajima R, Takao K, Huang S, Takano J, Iwata N, Miyakawa T et al.

    Molecular Brain (2008)

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  • Mice Lacking the kf-1 Gene Exhibit Increased Anxiety- but not Despair-Like Behavior

    Tsujimura A, Matsuki M, Takao K, Yamanishi K, Miyakawa T, Hashimoto-Gotoh T

    Frontiers in Behavioral Neuroscience (2008)

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  • Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity

    Pang P, Teng H, Zaitsev E, Woo N, Sakata K, Zhen S et al.

    Science (New York, N.Y.) (2004)

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  • 脳神経科学イラストレイテッド

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  • Enhanced susceptibility of audiogenic seizures in Fyn-kinase deficient mice

    Miyakawa T, Yagi T, Taniguchi M, Matsuura H, Tateishi K, Niki H

    Brain research. Molecular brain research (1995)

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  • Radial maze performance, open-field and elevated plus-maze behaviors in Fyn-kinase deficient mice: further evidence for increased fearfulness

    Miyakawa T, Yagi T, Kagiyama A, Niki H

    Brain research. Molecular brain research (1996)

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  • Increased fearfulness of Fyn tyrosine kinase deficient mice

    Miyakawa T, Yagi T, Watanabe S, Niki H

    Brain research. Molecular brain research (1994)

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  • Susceptibility to drug-induced seizures of Fyn tyrosine kinase-deficient mice

    Miyakawa T, Yagi T, Tateishi K, Niki H

    Neuroreport (1996)

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  • Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses

    Manabe T, Togashi H, Uchida N, Suzuki S, Hayakawa Y, Yamamoto M et al.

    Molecular and cellular neurosciences (2000)

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  • Abnormal synaptic transmission in the olfactory bulb of Fyn-kinase-deficient mice

    Kitazawa H, Yagi T, Miyakawa T, Niki H, Kawai N

    Journal of neurophysiology (1998)

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  • Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function

    Miyakawa T, Yagi T, Kitazawa H, Yasuda M, Kawai N, Tsuboi K et al.

    Science (New York, N.Y.) (1997)

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  • Differential effect of Fyn tyrosine kinase deletion on offensive and defensive aggression

    Miyakawa T, Yagi T, Takao K, Niki H

    Behavioural brain research (2001)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean

    Yamada M, Miyakawa T, Duttaroy A, Yamanaka A, Moriguchi T, Makita R et al.

    Nature (2001)

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  • Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures

    Kawai H, Allende M, Wada R, Kono M, Sango K, Deng C et al.

    The Journal of biological chemistry (2001)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Neurogranin null mutant mice display performance deficits on spatial learning tasks with anxiety related components

    Miyakawa T, Yared E, Pak J, Huang F, Huang K, Crawley J

    Hippocampus (2001)

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  • M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system

    Wess J, Duttaroy A, Zhang W, Gomeza J, Cui Y, Miyakawa T et al.

    Receptors & channels (2003)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory

    Zeng H, Chattarji S, Barbarosie M, Rondi-Reig L, Philpot B, Miyakawa T et al.

    Cell (2001)

    • -- Readers Readers not available. This publication is not currently accessible in the Mendeley catalog.
  • Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor

    Miyakawa T, Yamada M, Duttaroy A, Wess J

    J Neurosci (2001)

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  • Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia

    Miyakawa T, Leiter L, Gerber D, Gainetdinov R, Sotnikova T, Zeng H et al.

    Proc Natl Acad Sci U S A (2003)

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  • Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit

    Gerber D, Hall D, Miyakawa T, Demars S, Gogos J, Karayiorgou M et al.

    Proc Natl Acad Sci U S A (2003)

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  • [Stress and animal model of psychiatric disease]

    Miyakawa T, Yamasaki N

    Nippon yakurigaku zasshi. Folia pharmacologica Japonica (2005)

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  • Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice

    Miyamoto T, Morita K, Takemoto D, Takeuchi K, Kitano Y, Miyakawa T et al.

    The Journal of cell biology (2005)

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  • Acceleration of visually cued conditioned fear through the auditory pathway

    Newton J, Ellsworth C, Miyakawa T, Tonegawa S, Sur M

    Nature neuroscience (2004)

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  • NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21

    Arron J, Winslow M, Polleri A, Chang C, Wu H, Gao X et al.

    Nature (2006)

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  • Investigating gene-to-behavior pathways in psychiatric disorders: the use of a comprehensive behavioral test battery on genetically engineered mice

    Takao K, Miyakawa T

    Annals of the New York Academy of Sciences (2006)

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  • Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice

    Morishima Y, Miyakawa T, Furuyashiki T, Tanaka Y, Mizuma H, Nakanishi S

    Proceedings of the National Academy of Sciences of the United States of America (2005)

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  • Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi

    Hattori S, Hashimoto R, Miyakawa T, Yamanaka H, Maeno H, Wada K et al.

    Behavioural brain research (2007)

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  • Mouse liaison for integrative brain research

    Aiba A, Inokuchi K, Ishida Y, Itohara S, Kobayashi K, Masu M et al.

    Neuroscience research (2007)

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  • Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes

    Niemann S, Kanki H, Fukui Y, Takao K, Fukaya M, Hynynen M et al.

    The European journal of neuroscience (2007)

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  • Impact of brain-behavior phenotypying of genetically-engineered mice on research of neuropsychiatric disorders

    Takao K, Yamasaki N, Miyakawa T

    Neuroscience research (2007)

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  • Sept4, a component of presynaptic scaffold and Lewy bodies, is required for the suppression of alpha-synuclein neurotoxicity

    Ihara M, Yamasaki N, Hagiwara A, Tanigaki A, Kitano A, Hikawa R et al.

    Neuron (2007)

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  • Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion

    Shibata M, Yamasaki N, Miyakawa T, Kalaria R, Fujita Y, Ohtani R et al.

    Stroke; a journal of cerebral circulation (2007)

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  • Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2

    Sano H, Nagai Y, Miyakawa T, Shigemoto R, Yokoi M

    Journal of neurochemistry (2008)

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  • Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1

    Hung A, Futai K, Sala C, Valtschanoff J, Ryu J, Woodworth M et al.

    The Journal of neuroscience : the official journal of the Society for Neuroscience (2008)

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  • Altered sensitivities to morphine and cocaine in scaffold protein tamalin knockout mice

    Ogawa M, Miyakawa T, Nakamura K, Kitano J, Furushima K, Kiyonari H et al.

    Proceedings of the National Academy of Sciences of the United States of America (2007)

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  • M2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity

    Seeger T, Fedorova I, Zheng F, Miyakawa T, Koustova E, Gomeza J et al.

    The Journal of neuroscience : the official journal of the Society for Neuroscience (2004)

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Professional experience

Professor

Fujita Health University

April 2007 - Present

Education history

University of Tokyo

Ph. D.

March 1997 - Present