Graduate School of Medicine / School of Medicine, Faculty of Medicine

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Basic Medical Sciences

Neurobiology and Behavior

We teach pharmacology and neuroscience to medical students by lecture and practical training. Higher brain function including emotional behavior, learning, and memory is highly-developed in human. In addition, this function is the last frontier in the scientific field. In the medical sciences, neuronal and psychiatric disorders are ones of the most important academic fields. In our department, we seek to know the molecular mechanisms of the neuronal network formation, plasticity and maintenance regulated by “genetic information encoded in DNA” and “environmental learning information”. Thus, our goal is to understand the brain machinery integrating the signal pathway from genes to animal behavior.

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  • Research & education
  • Clinical Activities
  • Citizen Activities
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Associate Professor HANAMURA Kenji, Ph.D.
Assistant Professor YAMAZAKI Hiroyuki, Ph.D.

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Research & Education

Research content

Higher brain function including the emotional behavior, learning, and memory is highly-developed in human brain. In addition, this function is the last frontier in the modern world where the rate of scientific progress is accelerating. In our department, we are studying about (1) the molecular mechanisms of dendritic spine morphogenesis, (2) the role of cytoskeletons in the synaptic function, (3) the brain dysfunction such as those observed in Alzheimer’s disease, mood disorder, and schizophrenia caused by synaptic dysfunction. We study the above field with multidisciplinary techniques; such as the molecular and cellular biology, electrophysiology, behavioral analyses, pharmacology, and imaging-based techniques using a variety of materials including primary cultured neurons and gene-knockout animals.

Business education

(School of Medicine)
Pharmacology and Neuroscience (lecture and training), Medical and scientific writing (training), Writing of Tutorial Medical Paper (training), Basic Medicine Traning.

(Graduate School of Medicine)
Neurobiology and Behavior (lecture and training), In vitro neural monitoring training course (lecture and training), Technical Course for Live Imaging (lecture and training), Basic and clinical neuroscience lecture series (lecture), education of research (two graduate students)

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Clinical Activities

(no clinical assignments)

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Citizenship Activities

We help the organization of Brain Awareness Week (2000~) and Gunma prefectural Chuo secondary school. In addition, we help the foundation of KITA-KANTO BIO-FORUM to contribute to society.

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Yin XL, Jia QF, Zhang GY, Zhang JP, Shirao T, Jiang CX, Yin XY, Liu YS, Chen P, Gu XC, Qian ZK, Yin GZ, Sen Xia H, Hui L. “Association between decreased serum TBIL concentration and immediate memory impairment in schizophrenia patients.” Sci Rep. 2019 Feb 7;9(1):1622. doi: 10.1038/s41598-018-38227-6.

Daisuke Miki, Yuki Kobayashi, Tomoya Okada, Tatuso Miyamoto, Nobuyuki Takei, Yuko Sekino, Noriko Koganezawa, Tomoaki Shirao, Yumiko Saito “Characterization of functional primary cilia in human induced pluripotent stem cell-derived neurons.” Neurochem Res. 44(7):1736-1744. doi: 10.1007/s11064-019-02806-4.

Mitsuoka T, Hanamura K, Koganezawa N, Kikura-Hanajiri R, Sekino Y, Shirao T. “Assessment of NMDA receptor inhibition of phencyclidine analogues using a high-throughput drebrin immunocytochemical assay” J Pharmacol Toxicol Methods (2019) doi: 10.1016/j.vascn.2019.106583.

Hanamura K, Koganezawa N, Kamiyama K, Tanaka N, Oka T, Yamamura M, Sekino Y, Shirao T. “High-content imaging analysis for detecting the loss of drebrin clusters along dendrites in cultured hippocampal neurons.” J Pharmacol Toxicol Methods. 2019 Jul 2:106607. doi: 10.1016/j.vascn.2019.106607.

Miao S, Koganezawa N, Hanamura K, Puspitasari A, Shirao T. “N-methyl-D-aspartate receptor mediates X-irradiation-induced drebrin decrease in hippocampus” Kitakanto Medical Journal (2018) 68: 111-115

Hanamura K, Kamata Y, Yamazaki H, Kojima N, Shirao T, “Isoform-dependent regulation of drebrin dynamics in dendritic spines.” Neuroscience (2018) 379: 67-76

Yamazaki H, Sasagawa Y, Yamamoto H, Bito H, Shirao T. “CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools” J. Neurochem.(2018) 146:145-159.

Yasuda H, Kojima N, Yamazaki H, Hanamura K, Sakimura K, Shirao T. “Drebrin isoforms critically regulate NMDAR- and mGluR-dependent LTD induction” Front Cell Neurosci. 2018 Oct 8;12:330. doi: 10.3389/fncel.2018.00330.

小金澤紀子、花村健次、白尾智明、「ヒトiPS細胞由来神経細胞を用いた医薬品評価系の現状について」日本薬理学雑誌 149: 104-109 (2017)

Shirao T, Hanamura K, Koganezawa N, Ishizuka Y, Yamazaki H, Sekino Y. “The role of drebrin in neurons” . J. Neurochem. (2017) 141(6):819-834. doi: 10.1111/jnc.13988. Epub 2017 Apr 21. Review. (Free Acess)

Koganezawa N, Hanamura K, Sekino Y, Shirao T. “The role of drebrin in dendritic spines” Mol Cell Neurosci. 2017 Oct;84:85-92. doi: 10.1016/j.mcn.2017.01.004.(Open Access)

Li B, Ding S, Feng N, Mooney N, Ooi YS, Renf L, Diep J, Kelly MR, Yasukawa LL, Patton JT, Yamazaki H, Shirao T, Jackson PK, Greenberg HB. “Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis.” Proc Natl Acad Sci U S A, (2017) Apr 17. pii: 201619266. doi: 10.1073/pnas.1619266114.

Kajita Y, Kojima N, Koganezawa N, Yamazaki H, Sakimura K, Shirao T. “Drebrin E regulates neuroblast proliferation and chain migration in the adult brain “ Eur J Neurosci. 2017 Sep;46(6):2214-2228.

Hanamura K, Washburn HR, Sheffler-Collins SI, Xia NL, Henderson N, Tillu DV, Hassler S, Spellman DS, Zhang G, Neubert TA, Price TJ, Dalva MB “ Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain.” PLoS Biol. 2017 Jul 18;15(7):e2002457.

Shirao T., Sekino Y. (Eds.) (2017) Drebrin. (Advances in Experimental Medicine and Biology, vol 1006) Tokyo, Springer

Sekino Y, Koganezawa N, Mizui T, Shirao T. “Role of Drebrin in Synaptic Plasticity” Adv Exp Med Biol. 2017;1006:183-201. doi: 10.1007/978-4-431-56550-5_11.

Yamazaki H, Shirao T. “Homer, Spikar, and Other Drebrin-Binding Proteins in the Brain”Adv Exp Med Biol. 2017;1006:249-268. doi: 10.1007/978-4-431-56550-5_14

Shirao T, Koganezawa N, Yamazaki H, Hanamura K, Imamura K. “Localization of Drebrin: Light Microscopy Study” Adv Exp Med Biol. 2017;1006:105-118. doi: 10.1007/978-4-431-56550-5_7

Shirao T, Sekino Y. “General Introduction to Drebrin” Adv Exp Med Biol. 2017;1006:3-22. doi: 10.1007/978-4-431-56550-5_1.

Ishizuka Y, Hanamura K. “Drebrin in Alzheimer’s Disease” Adv Exp Med Biol. 2017;1006:203-223. doi: 10.1007/978-4-431-56550-5_12.

Hanamura K. “Drebrin in Neuronal Migration and Axonal Growth” Adv Exp Med Biol. 2017;1006:141-155. doi: 10.1007/978-4-431-56550-5_9.

Fujieda T, Koganezawa N, Ide Y, Shirao T and Sekino Y. “An Inhibitory Pathway Controlling the Gating Mechanism of the Mouse Lateral Amygdala Revealed by Voltage-Sensitive Dye Imaging.” Neuroscience Letters 590:126-131(2015)

Shi-Qiong Xu, Simone Buraschi, Alaide Morcavallo, Marco Genua, Tomoaki Shirao, Stephen C. Peiper, Leonard G. Gomella, Ruth Birbe, Antonino Belfiore, Renato V. Iozzo and Andrea Morrione “A novel role for drebrin in regulating progranulin bioactivity in urothelial cancer.” Oncotarget 6:10825-39 (2015)

Ishizuka Y, Shimizu H, Takagi E, Kato M, Yamagata H, Mikuni M, Shirao T. “Histone deacetylase mediates the decrease in drebrin cluster density induced by amyloid beta oligomers.” Neurochem Int. 76:114-121 (2014)

Tanabe K, Yamazaki H, Inaguma Y, Asada A, Kimura T, Takahashi J, Taoka M, Ohshima T, Furuichi T, Isobe T, Nagata K, Shirao T, Hisanaga S. “Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration.” PLoS One. 9:e92291 (2014)

Ishikawa M, Shiota J, Ishibashi1 Y, Hakamata T, Shoji S, Fukuchi M, Masaaki Tsuda M, Shirao T, Sekino Y, Baraban JM and Tabuchi A. “Cellular localization and dendritic function of rat isoforms of the SRF coactivator MKL1 in cortical neurons.” NeuroReport. 25:585-592 (2014)

Mizui T,Sekino Y, Yamazaki H, Ishizuka Y, Takahashi H, Kojima N, Kojima M and Shirao T.“Myosin Ⅱ ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines” PLoS ONE 9 (1): e85367 (2014)

Yamazaki H, Kojima N, Kato K, Hirose H, Iwasaki T, Mizui T, Takahashi H, Hanamura K, Roppongi RT, Koibuchi N, Sekino Y, Mori N, Shirao T. “Spikar, a novel drebrin-binding protein, regulates the formation and stabilization of dendritic spines”. J Neurochem. 128:507-522 (2013)

白尾智明、山崎博幸「樹状突起棘(スパイン)のアクチンフィラメントと微小管」 Clinical Neuroscience 31: 1302-1395(2013)

Mitsuru Ishikawa, Jun Shiota, Yuta Ishibashi, Tomoyuki Hakamata, Shizuku Shoji, Mamoru Fukuchi, Masaaki Tsuda, Tomoaki Shirao, Yuko Sekino, Toshihisa Ohtsuka, Jay M. Baraban and Akiko Tabuchi. “Identification, expression and characterization of rat isoforms of the SRF coactivator MKL1.”FEBS Open Bio. 3:387-393 (2013)

Yuta Ishizuka, Naomasa Kakiya, Lee A. Witters, Noriko Oshiro, Tomoaki Shirao, Hiroyuki Nawa and Nobuyuki Takei “AMP-activated protein kinase (AMPK) counteractsbrain-derived neurotrophic factor (BDNF)-induced mammalian target of rapamycin complex 1 (mTORC1) signaling in neurons “J Neurochem. 127:66-77 (2013)

Shirao T, Gonzalez-Billault C “Actin filaments and microtubules in dendritic spines”.J eurochem. 126:155-164. (2013)

Roppongi RT, Kojima N, Hanamura K, Yamazaki H, Shirao T. “Selective reduction of drebrin and actin in dendritic spines of hippocampal neurons by activation of 5-HT2A receptors.” Neurosci Lett. 547:76-81 (2013)

K Shirai, T Mizui, Y Suzuki, M Okamoto, K Hanamura, Y Yoshida, M Hino, S Noda, W S. AL-Jahdari, A Chakravarti, T Shirao, T Nakano, “X-Irradiation Changes Dendritic Spine Morphology and Density through Reduction of Cytoskeletal Proteins in Mature Neurons” Radiation Research. 179:630-636 (2012)

C.B. Canto, N. Koganezawa, P. Beed, E.I. Moser, M.P. Witter. All layers of medial entorhinal cortex receive presubicular and parasubicular inputs. J.Neuroscience, 32: 17620-17631 (2012)

Kenichi Kato, Tomoaki Shirao, Hiroyuki Yamazaki, Kazuyuki Imamura, and Yuko Sekino. “Regulation of AMPA receptor recruitment by the actin binding protein drebrin in cultured hippocampal neurons.” J. Neurosci. Neuroeng. 1: 153-160 (2012)

Tanaka K, Sato K, Yoshida T, Fukuda T, Hanamura K, Kojima N, Shirao T, Yanagawa T, and Watanabe H. “Evidence for cell density affecting C2C12 myogenesis: possible regulation of myogenesis by cell-cell communication.” Muscle and Nerve, 44:968-977 ( 2011)

Kobayashi-Yamazaki C, Shirao T, Sasagawa Y, Maruyama Y, Akita H, Saji M, and Sekino Y. “Lesions of the supramammillary nucleus decrease self-grooming behavior of rats placed in an open field” The Kitakanto Medical Jorunal , 61:287-292 ( 2011)

Han W, Takamatsu Y, Yamamoto H, Kasai S, Endo S, Shirao T, Kojima N, Ikeda K. “Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization” PLoS ONE in press

Okamoto T,, Endo S, Shirao T, and Nagao S. “Role of Cerebellar Cortical Protein Synthesis in Transfer of Memory Trace of Cerebellum-Dependent Motor Learning” J. Neurosci. 31:8958-66.

Kambe T, Motoi Y, Inoue R, Kojima N, Tada N, Kimura T, Sahara N, Yamashita S, Mizoroki T, Takashima A, Shimada K, Ishiguro K, Mizuma H, Onoe H, Mizuno Y, Hattori N “Differential regional distribution of phosphorylated tau and synapse loss in the nucleus accumbens in tauopathy model mice.” Neurobiol Dis. 42:404-414. (2011)

Kaminuma T, Suzuki Y, Shirai K, Mizui T, Noda S, Yosida Y, Funayama T, Takahasi T, Kobayashi Y, Shirao T, Nakano T. “Effectiveness of carbon-ion beams for apoptosis induction in rat primary immature hippocampal neurons” J. Rad. Res. 51:627-631 (2010)

Hanamura, K, Mizui T, Kakizaki T, Roppongi TR, Yamazaki H, Yanagawa Y, Shirao T. “Low accumulation of drebrin at glutamatergic postsynaptic sites on GABAergic neurons” Neuroscience 169: 1489-1500 (2010)

Perez-Martinez M, Gordon-Alonso M, Cabrero JR, Barrero-Villar M, Rey M, Mittelbrunn M, Lamana A, Morlino G, Calabia C, Yamazaki H, Shirao T, Vazquez J, Gonzalez-Amaro R, Veiga E, Sanchez-Madrid F. “F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse” J. Cell Sci. 123:1160-1170 (2010)

Mercer JC, Mottram LF Qi Q, Lee YC, Bruce D, Iyer A, Yamazaki H, Shirao T, Choe MH,. Peterson BR, August A “Chemico-Genetic Identification of Drebrin as a Regulator of Calcium Responses.” Int. J. Biochem. Cell Biol. 42:337-345 (2010)

Kojima N, Hanamura K, Yamazaki H, Ikeda T, Itohara S, Shirao T. “Genetic disruption of the alternative splicing of drebrin gene impairs context-dependent fear learning in adulthood” Neuroscience 165: 138-150 (2010)

Okamoto M, Suzuki Y, Shirai K, Mizui T, Yoshida Y, Noda S,. Al-Jahdari WS, Shirao T, Nakano T. “Effect of Irradiation on the Development of Immature Hippocampal Neurons In Vitro” Radiat Res 172:718-724 (2009)

Aoki C, Kojima N, Sabaliauskas N, Shah L, Oakford J, Ahmed T, Yamazaki H, Hanamura K, Shirao T “Drebrin A Knock-Out Eliminates the Rapid Form of Homeostatic Synaptic Plasticity at Excitatory Synapses of Intact Adult Cerebral Cortex” J Comp Neurol 517:105-121 (2009)

Ito M, Shirao T, Doya K, Sekino Y. “Three-dimensional distribution of Fos-positive neurons in the supramammillary nucleus of the rat exposed to novel environment.” Neurosci. Res. 64:397-402 (2009)

Mizui T., Kojima N, Yamazaki H, Katayama M, Hana mura K, Shirao T. “Drebrin E is involved in the mechanism regulating axonal growth through actin-myosin interactions.” J Neurochem 109:611-622 (2009).

Takahashi, T, Yamazaki, H, Hanamura K, Sekino Y and Shirao T “AMPA receptor inhibition causes abnormal dendritic spines by destabilizing drebrin” J Cell Sci. 122:1211-1229 (2009)

Ivanov A, Esclapez M, Pellegrino1 C, Tomoaki Shirao T, and Ferhat L. “Drebrin A regulates the dendritic spine plasticity and synaptic function in cultured hippocampal neurons” J. Cell Sci. 122: 524-534 (2009)

Kojima N, Borlikova G, Sakamoto T, Yamada K, Ikeda T, Itohara S, Niki H, Endo S: Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory. J Neurosci. 28:6459-6472 (2008)

Song M, Kojima N, Hanamura K, Sekino Y, Inoue KH, Mikuni M, Shirao T, “Expression of drebrin E in migrating neuroblasts in adult rat brain: coincidence between drebrin E disappearance from cell body and cessation of migration.” Neuroscience 152:670-682 (2008)

Kobayashi, C., Aoki, C., Kojima, N., Yamazaki, H., and Shirao, T., “Drebrin A content correlates with spine head size in the adult mouse cerebral cortex” J. Comp. Neurol. in press

Sekino Y, Kojima N, Shirao T. “Role of actin cytoskeleton in dendritic spine morphogenesis” Neurochem. Int. in press

Kato, K., Sekino, Y., Takahashi, H., Yasuda, H., Shirao, T., “Increase of AMPA receptors-mediated miniature EPSC amplitude after chronic NMDA receptor blockade in cultured hippocampal neurons” Neurosci. Lett. 418: 4-8 (2007)

Kojima, N., Shirao, T. “Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex: the study of neurological disorders accompanied by cognitive deficits.” Neurosci. Res. 58: 1-5 (2007)

Majoul, I., Shirao, T., Sekino, Y., Duden, R. “Many faces of Drebrin: from building dendritic spines and stabilizing gap junctions to shaping neurite-like cell processes” Histochem. Cell Biol. 127: 355-361 (2007)

Shirai, K., Mizui, T., Suzuki, Y., Kobayashi, Y., Nakano, T., Shirao, T. “Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro.” Neurosci. Lett. 399: 57-60 (2006)

Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul, V., Shirao, T., Aoki, C., Huerta, P.T. “AMPA receptor downscaling at the onset of Alzheimer’s pathology in double knock-in mice” Proc. Natl. Acad. Sci. (USA) 103: 3410-3415 (2006)

Fujisawa, S., Shirao, T., Aoki, C. “In vivo, competitive blockade of NMDA receptors induces rapid shape change of post-synaptic spines and F-actin reorganization within dendritic spines of adult rat cortex.” Neuroscience 140:1177-1187 (2006)

Takahashi, H., Mizui T. and Shirao, T. “Downregulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurons” J. Neuochem 97(s1):110-115 (2006)

Sekino, Y., Tanaka, S., Hanamura, K., Yamazaki, H., Sasagawa, Y., Xue Y., Hayashi, K., and Shirao, T. “Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution: disappearance from dendritic spines and appearance in dendritic shafts” Mol. Cell. Neurosci. 31: 493-504 (2006)

Mahadomrongkul, V., Huerta, P.T., Shirao, T., Aoki, C. “Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PS1 genes” Brain Res. 1064: 66-74 (2005)

Mizui, T., Takahashi, H., Sekino, Y., and Shirao, T. “Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions.” Mol. Cell. Neurosci. 30: 149-157 (2005)

Aoki, C., Sekino, Y., Hanamura, K., Fujisawa, S., Mahadomrongkul, V., Ren, Y., and Shirao, T. “Drebrin A is a Postsynaptic Protein that Localizes in vivo to the Submembranous Surface of Dendritic Sites Forming Excitatory Synapses” J. Comp. Neurol. 483: 383-402 (2005)

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Tomoaki Shirao came to Gunma University as professor from Keio University School of Medicine, Department of Physiology and Kensuke Hayashi was transferred as Research Associate. They started the research of drebrin in neuronal dendritic spine.

Yuko Sekino joined as Research Associate, and started to analyze the signaling flow of a local circuit in hippocampus. Satoshi Tanaka entered as graduate school student.

Hiroyuki Yamazaki joined as graduate school student.

Kensuke Hayashi moved to Institute for Molecular and Cellular Regulation (Gunma University) as Associate Professor, and Yoshiko Saito joined as Research Associate

Yuko Sekino was promoted to Assistant Professor. Yoshiko Saito moved, and Jin Minghao and Satoshi Tanaka were adopted as Research Associate.

Jin Minghao moved, and Hiroyuki Yamazaki took up his new post as Research Associate.

Yuko Sekino was promoted to Associate Professor.

Organizational affiliation was changed from “Department of Neurobiology and Behavior, Gunma University School of Medicine” to “Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine”. Satoshi Tanaka moved, and Kenji Hanamura joined as Research Associate.

Yuko Sekino moved to Institute of Medical Science (University of Tokyo) as Associate Professor, and Nobuhiko Kojima joined as Assistant Professor.

Hideto Takahashi joined as Research Associate in Education and Research Center of Graduate School of Medicine.

Nobuhiko Kojima was promoted to Associate Professor.

Kenji Hanamura moved, and Yuta Ishizuka joined as Assistant Professor.

Noriko Koganezawa joined as Assistant Professor in Education and Research Support Center of Graduate school of Medicine.

Nobuhiko Kojima moved to Faculty of Life Sciences (Toyo University) as Professor.

Reiko Roppongi joined as Assistant Professor.

Reiko Roppongi moved, and Kenji Hanamura joined as Assistant Professor.

Yuta Ishizuka moved, and Noriko Koganezawa became Assistant Professor in Department of Neurobiology and Behavior.

Kenji Hanamura was promoted to Associate Professor.