Updated on 2025/10/09

写真a

 
TERUNUMA Miho
 
Organization
Academic Assembly Institute of Medicine and Dentistry SHIGAKU KEIRETU Professor
Graduate School of Medical and Dental Sciences Oral Life Science Tissue Regeneration and Reconstruction Professor
Title
Professor
External link

Degree

  • 高等教育学（Postgraduate Certificate in Academic Practice in Higher Education） ( 2016.2   英国　レスター大学 )

  • 博士（歯学） ( 2004.3   九州大学 )

  • 歯学士 ( 2000.3   九州大学 )

Research Areas

  • Life Science / Neuroscience-general

  • Life Science / Oral biological science

  • Life Science / Oral pathobiological science

Research History (researchmap)

  • Niigata University   Graduate School of Medical and Dental Sciences   Professor

    2016.8

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  • University of Leicester, College of Medicine, Biological Sciences and Psychology   Department of Neuroscience, Psychology and Behaviour   Lecturer in Neuroscience

    2013.10 - 2016.7

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  • Tufts University   Department of Neuroscience   Research Associate

    2009.7 - 2013.10

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  • Tufts University   Department of Neuroscience   Postdoctoral Associate

    2008.7 - 2009.6

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  • University of Pennsylvania   Department of Neuroscience   Postdoctoral Fellow

    2005.8 - 2008.7

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  • Kyushu University   Faculty of Dental Science

    2005.4 - 2005.7

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  • Kyushu University   Faculty of Dental Science

    2003.4 - 2005.3

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Research History

  • Niigata University   Graduate School of Medical and Dental Sciences Oral Life Science Tissue Regeneration and Reconstruction   Professor

    2016.8

 

Papers

  • Scratch-Based Isolation of Primary Cells (SCIP): A Novel Method to Obtain a Large Number of Human Dental Pulp Cells Through One-Step Cultivation

    Yuki Kiyokawa, Masahiko Terajima, Masahiro Sato, Emi Inada, Yuria Hori, Ryo Bando, Yoko Iwase, Naoko Kubota, Tomoya Murakami, Hiroko Tsugane, Satoshi Watanabe, Takahiro Sonomura, Miho Terunuma, Takeyasu Maeda, Hirofumi Noguchi, Issei Saitoh

    Journal of Clinical Medicine   13 ( 23 )   7058 - 7058   2024.11

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Background: Dental pulp (DP) is a connective tissue composed of various cell types, including fibroblasts, neurons, adipocytes, endothelial cells, and odontoblasts. It contains a rich supply of pluripotent stem cells, making it an important resource for cell-based regenerative medicine. However, current stem cell collection methods rely heavily on the enzymatic digestion of dissected DP tissue to isolate and propagate primary cells, which often results in low recovery rates and reduced cell survival, particularly from deciduous teeth. Methods: We developed a novel and efficient method to obtain a sufficient number of cells through a one-step cultivation process of isolated DP. After the brief digestion of DP with proteolytic enzymes, it was scratched onto a culture dish and cultured in a suitable medium. By day 2, the cells began to spread radially from DP, and by day 10, they reached a semi-confluent state. Cells harvested through trypsinization consistently yielded over 1 million cells, and after re-cultivation, the cells could be propagated for more than ten passages. Results: The proliferative and differentiation capacities of the cells after the 10th passage were comparable to those from the first passage. The cells expressed alkaline phosphatase as an undifferentiation marker. Similarly, they also maintained the constitutive expression of stem cell-specific markers and differentiation-related markers, even after the 10th passage. Conclusions: This method, termed “scratch-based isolation of primary cells from human dental pulps (SCIP)”, enables the efficient isolation of a large number of DP cells with minimal equipment and operator variability, while preserving cell integrity. Its simplicity, high success rate, and adaptability for patients with genetic diseases make it a valuable tool for regenerative medicine research and clinical applications.

    DOI： 10.3390/jcm13237058

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  • Behavioral analysis of kainate receptor KO mice and the role of GluK3 subunit in anxiety. Reviewed International journal

    Izumi Iida, Kohtarou Konno, Rie Natsume, Manabu Abe, Masahiko Watanabe, Kenji Sakimura, Miho Terunuma

    Scientific reports   14 ( 1 )   4521 - 4521   2024.2

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Kainate receptors (KARs) are one of the ionotropic glutamate receptors in the central nervous system (CNS) comprised of five subunits, GluK1-GluK5. There is a growing interest in the association between KARs and psychiatric disorders, and there have been several studies investigating the behavioral phenotypes of KAR deficient mice, however, the difference in the genetic background has been found to affect phenotype in multiple mouse models of human diseases. Here, we examined GluK1-5 single KO mice in a pure C57BL/6N background and identified that GluK3 KO mice specifically express anxiolytic-like behavior with an alteration in dopamine D2 receptor (D2R)-induced anxiety, and reduced D2R expression in the striatum. Biochemical studies in the mouse cortex confirmed that GluK3 subunits do not assemble with GluK4 and GluK5 subunits, that can be activated by lower concentration of agonists. Overall, we found that GluK3-containing KARs function to express anxiety, which may represent promising anti-anxiety medication targets.

    DOI： 10.1038/s41598-024-55063-z

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  • The Role of Genetically Modified Human Feeder Cells in Maintaining the Integrity of Primary Cultured Human Deciduous Dental Pulp Cells. Reviewed International journal

    Natsumi Ibano, Emi Inada, Shinji Otake, Yuki Kiyokawa, Kensuke Sakata, Masahiro Sato, Naoko Kubota, Hirofumi Noguchi, Yoko Iwase, Tomoya Murakami, Tadashi Sawami, Yoshito Kakihara, Takeyasu Maeda, Miho Terunuma, Yutaka Terao, Issei Saitoh

    Journal of clinical medicine   11 ( 20 )   2022.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    Tissue-specific stem cells exist in tissues and organs, such as skin and bone marrow. However, their pluripotency is limited compared to embryonic stem cells. Culturing primary cells on plastic tissue culture dishes can result in the loss of multipotency, because of the inability of tissue-specific stem cells to survive in feeder-less dishes. Recent findings suggest that culturing primary cells in medium containing feeder cells, particularly genetically modified feeder cells expressing growth factors, may be beneficial for their survival and proliferation. Therefore, the aim of this study was to elucidate the role of genetically modified human feeder cells expressing growth factors in maintaining the integrity of primary cultured human deciduous dental pulp cells. Feeder cells expressing leukemia inhibitory factor, bone morphogenetic protein 4, and basic fibroblast growth factor were successfully engineered, as evidenced by PCR. Co-culturing with mitomycin-C-treated feeder cells enhanced the proliferation of newly isolated human deciduous dental pulp cells, promoted their differentiation into adipocytes and neurons, and maintained their stemness properties. Our findings suggest that genetically modified human feeder cells may be used to maintain the integrity of primary cultured human deciduous dental pulp cells.

    DOI： 10.3390/jcm11206087

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  • Ammonia induces amyloidogenesis in astrocytes by promoting amyloid precursor protein translocation into the endoplasmic reticulum. Reviewed International journal

    Ayaka Komatsu, Izumi Iida, Yusuke Nasu, Genki Ito, Fumiko Harada, Sari Kishikawa, Stephen J Moss, Takeyasu Maeda, Miho Terunuma

    The Journal of biological chemistry   298 ( 5 )   101933 - 101933   2022.5

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    Hyperammonemia is known to cause various neurological dysfunctions such as seizures and cognitive impairment. Several studies have suggested that hyperammonemia may also be linked to the development of Alzheimer's disease (AD). However, the direct evidence for a role of ammonia in the pathophysiology of AD remains to be discovered. Herein, we report that hyperammonemia increases the amount of mature amyloid precursor protein (mAPP) in astrocytes, the largest and most prevalent type of glial cells in the central nervous system that are capable of metabolizing glutamate and ammonia, and promotes amyloid beta (Aβ) production. We demonstrate the accumulation of mAPP in astrocytes was primarily due to enhanced endocytosis of mAPP from the plasma membrane. A large proportion of internalized mAPP was targeted not to the lysosome, but to the endoplasmic reticulum, where processing enzymes β-secretase BACE1 (beta-site APP cleaving enzyme 1) and γ-secretase presenilin-1 are expressed, and mAPP is cleaved to produce Aβ. Finally, we show the ammonia-induced production of Aβ in astrocytic endoplasmic reticulum was specific to Aβ42, a principal component of senile plaques in AD patients. Our studies uncover a novel mechanism of Aβ42 production in astrocytes and also provide the first evidence that ammonia induces the pathogenesis of AD by regulating astrocyte function.

    DOI： 10.1016/j.jbc.2022.101933

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  • Perivascular Hedgehog responsive cells play a critical role in peripheral nerve regeneration via controlling angiogenesis. Reviewed International journal

    Yurie Yamada, Jun Nihara, Supaluk Trakanant, Takehisa Kudo, Kenji Seo, Izumi Iida, Kenji Izumi, Masayuki Kurose, Yutaka Shimomura, Miho Terunuma, Takeyasu Maeda, Atsushi Ohazama

    Neuroscience research   173   62 - 70   2021.6

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    Hh signaling has been shown to be activated in intact and injured peripheral nerve. However, the role of Hh signaling in peripheral nerve is not fully understood. In the present study, we observed that Hh signaling responsive cells [Gli1(+) cells] in both the perineurium and endoneurium. In the endoneurium, Gli1(+) cells were classified as blood vessel associated or non-associated. After injury, Gli1(+) cells around blood vessels mainly proliferated to then accumulate into the injury site along with endothelial cells. Hh signaling activity was retained in Gli1(+) cells during nerve regeneration. To understand the role of Hedgehog signaling in Gli1(+) cells during nerve regeneration, we examined mice with Gli1(+) cells-specific inactivation of Hh signaling (Smo cKO). After injury, Smo cKO mice showed significantly reduced numbers of accumulated Gli1(+) cells along with disorganized vascularization at an early stage of nerve regeneration, which subsequently led to an abnormal extension of the axon. Thus, Hh signaling in Gli1(+) cells appears to be involved in nerve regeneration through controlling new blood vessel formation at an early stage.

    DOI： 10.1016/j.neures.2021.06.003

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  • A comparative analysis of kainate receptor GluK2 and GluK5 knockout mice in a pure genetic background Reviewed International journal

    Izumi Iida, Kohtarou Konno, Rie Natsume, Manabu Abe, Masahiko Watanabe, Kenji Sakimura, Miho Terunuma

    Behavioural Brain Research   405   113194 - 113194   2021.5

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

    Kainate receptors (KARs) are members of the glutamate receptor family that regulate synaptic function in the brain. Although they are known to be associated with psychiatric disorders, how they are involved in these disorders remains unclear. KARs are tetrameric channels assembled from a combination of GluK1-5 subunits. Among these, GluK2 and GluK5 subunits are the major heteromeric subunits in the brain. To determine the functional similarities and differences between GluK2 and GluK5 subunits, we generated GluK2 KO and GluK5 KO mice on a C57BL/6N background, a well-characterized inbred strain, and compared their behavioral phenotypes. We found that GluK2 KO and GluK5 KO mice exhibited the same phenotypes in many tests, such as reduced locomotor activity, impaired motor function, and enhanced depressive-like behavior. No change was observed in motor learning, anxiety-like behavior, or sociability. Additionally, we identified subunit-specific phenotypes, such as reduced motivation toward their environment in GluK2 KO mice and an enhancement in the contextual memory in GluK5 KO mice. These results revealed that GluK2 and GluK5 subunits not only function in a coordinated manner but also have a subunit-specific role in regulating behavior. To summarize, we demonstrated subunit-specific and common behavioral effects of GluK2 and GluK5 subunits for the first time. Moreover, to the best of our knowledge, this is the first evidence of the involvement of the GluK5 subunit in the expression of depressive-like behavior and contextual memory, which strongly indicates its role in psychiatric disorders.

    DOI： 10.1016/j.bbr.2021.113194

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  • Drug-Induced Naïve iPS Cells Exhibit Better Performance than Primed iPS Cells with Respect to the Ability to Differentiate into Pancreatic β-Cell Lineage. Reviewed International journal

    Yuki Kiyokawa, Masahiro Sato, Hirofumi Noguchi, Emi Inada, Yoko Iwase, Naoko Kubota, Tadashi Sawami, Miho Terunuma, Takeyasu Maeda, Haruaki Hayasaki, Issei Saitoh

    Journal of clinical medicine   9 ( 9 )   2020.9

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    Pluripotent stem cells are classified as naïve and primed cells, based on their in vitro growth characteristics and potential to differentiate into various types of cells. Human-induced pluripotent stem cells (iPSCs, also known as epiblast stem cells [EpiSCs]) have limited capacity to differentiate and are slightly more differentiated than naïve stem cells (NSCs). Although there are several in vitro protocols that allow iPSCs to differentiate into pancreatic lineage, data concerning generation of β-cells from these iPSCs are limited. Based on the pluripotentiality of NSCs, it was hypothesized that NSCs can differentiate into pancreatic β-cells when placed under an appropriate differentiation induction condition. We examined whether NSCs can be efficiently induced to form potentially pancreatic β cells after being subjected to an in vitro protocol. Several colonies resembling in vitro-produced β-cell foci, with β-cell-specific marker expression, were observed when NSC-derived embryoid bodies (EBs) were induced to differentiate into β-cell lineage. Conversely, EpiSC-derived EBs failed to form such foci in vitro. Intrapancreatic grafting of the in vitro-formed β-cell foci into nude mice (BALB/c-nu/nu) generated a cell mass containing insulin-producing cells (IPCs), without noticeable tumorigenesis. These NSCs can be used as a promising resource for curing type 1 diabetes.

    DOI： 10.3390/jcm9092838

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  • Sustained laryngeal transient receptor potential vanilloid 1 activation inhibits mechanically induced swallowing in anesthetized rats. Reviewed International journal

    Midori Yoshihara, Takanori Tsujimura, Taku Suzuki, Kouta Nagoya, Naru Shiraishi, Jin Magara, Miho Terunuma, Makoto Inoue

    American journal of physiology. Gastrointestinal and liver physiology   319 ( 3 )   G412-G419   2020.9

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    A major component of gastric acid is hydrochloric acid (HCl), which can activate transient receptor potential vanilloid 1 (TRPV1). In the present study, we investigated how sustained laryngeal TRPV1 activation affects the frequency of the swallowing reflex. Experiments were carried out on 85 male Sprague-Dawley rats. The effects of short and sustained application of chemicals (3 µl of 0.1 N HCl or capsaicin) on the frequency of swallowing and on time-dependent changes in the occurrence of swallowing evoked by supralaryngeal nerve stimulation were determined. To evaluate vascular permeability of the larynx, Evans blue dye was intravenously injected after 5 or 60 min of sustained TRPV1 activation. SB366791 (a TRPV1 inhibitor) and Cap/QX-314 (a TRPV1-expressed neuronal inhibitor) significantly inhibited HCl/capsaicin-induced swallowing, but air flow-induced swallowing was not affected. Although the number of air flow-induced swallows followed by capsaicin stimulation was not affected within 5 min, it was significantly reduced by 60-min capsaicin or HCl application. The swallowing threshold associated with supralaryngeal nerve stimulation did not significantly change throughout the recording period. Evans blue dye concentrations in the larynx were significantly higher at 60 min in the 10-5 M capsaicin group than in the control group. Our results suggest that sustained TPRV1 activation not only desensitizes TRPV1 but also inactivates mechanoreceptors, which may be attributed to increases in vascular permeability and edema, as part of an inflammatory process.NEW & NOTEWORTHY Although a transient receptor potential vanilloid 1 (TRPV1) inhibitor or TRPV1-expressed neuronal inhibitor significantly inhibited HCl/capsaicin-evoked swallowing, air flow-induced swallowing was not affected. The number of air flow-induced swallows was significantly reduced within 60 min of TRPV1 activation. Evans blue dye concentration in the larynx increased 60 min after capsaicin application. TPRV1 activation not only desensitizes TRPV1 but also inactivates mechanoreceptors caused by increases in vascular permeability and edema.

    DOI： 10.1152/ajpgi.00082.2020

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  • Direct Interaction of PP2A Phosphatase with GABAB Receptors Alters Functional Signaling. Reviewed International journal

    Xiaofan Li, Miho Terunuma, Tarek G Deeb, Shari Wiseman, Menelas N Pangalos, Angus C Nairn, Stephen J Moss, Paul A Slesinger

    The Journal of neuroscience : the official journal of the Society for Neuroscience   40 ( 14 )   2808 - 2816   2020.4

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    Addictive drugs usurp the brain's intrinsic mechanism for reward, leading to compulsive and destructive behaviors. In the ventral tegmental area (VTA), the center of the brain's reward circuit, GABAergic neurons control the excitability of dopamine (DA) projection neurons and are the site of initial psychostimulant-dependent changes in signaling. Previous work established that cocaine/methamphetamine exposure increases protein phosphatase 2A (PP2A) activity, which dephosphorylates the GABABR2 subunit, promotes internalization of the GABAB receptor (GABABR) and leads to smaller GABABR-activated G-protein-gated inwardly rectifying potassium (GIRK) currents in VTA GABA neurons. How the actions of PP2A become selective for a particular signaling pathway is poorly understood. Here, we demonstrate that PP2A can associate directly with a short peptide sequence in the C terminal domain of the GABABR1 subunit, and that GABABRs and PP2A are in close proximity in rodent neurons (mouse/rat; mixed sexes). We show that this PP2A-GABABR interaction can be regulated by intracellular Ca2+ Finally, a peptide that potentially reduces recruitment of PP2A to GABABRs and thereby limits receptor dephosphorylation increases the magnitude of baclofen-induced GIRK currents. Thus, limiting PP2A-dependent dephosphorylation of GABABRs may be a useful strategy to increase receptor signaling for treating diseases.SIGNIFICANCE STATEMENT Dysregulation of GABAB receptors (GABABRs) underlies altered neurotransmission in many neurological disorders. Protein phosphatase 2A (PP2A) is involved in dephosphorylating and subsequent internalization of GABABRs in models of addiction and depression. Here, we provide new evidence that PP2A B55 regulatory subunit interacts directly with a small region of the C-terminal domain of the GABABR1 subunit, and that this interaction is sensitive to intracellular Ca2+ We demonstrate that a short peptide corresponding to the PP2A interaction site on GABABR1 competes for PP2A binding, enhances phosphorylation GABABR2 S783, and affects functional signaling through GIRK channels. Our study highlights how targeting PP2A dependent dephosphorylation of GABABRs may provide a specific strategy to modulate GABABR signaling in disease conditions.

    DOI： 10.1523/JNEUROSCI.2654-19.2020

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  • Repeated human deciduous tooth-derived dental pulp cell reprogramming factor transfection yields multipotent intermediate cells with enhanced iPS cell formation capability. Reviewed International journal

    Miki Soda, Issei Saitoh, Tomoya Murakami, Emi Inada, Yoko Iwase, Hirofumi Noguchi, Shinji Shibasaki, Mie Kurosawa, Tadashi Sawami, Miho Terunuma, Naoko Kubota, Yutaka Terao, Hayato Ohshima, Haruaki Hayasaki, Masahiro Sato

    Scientific reports   9 ( 1 )   1490 - 1490   2019.2

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    Human tissue-specific stem cells (hTSCs), found throughout the body, can differentiate into several lineages under appropriate conditions in vitro and in vivo. By transfecting terminally differentiated cells with reprogramming factors, we previously produced induced TSCs from the pancreas and hepatocytes that exhibit additional properties than iPSCs, as exemplified by very low tumour formation after xenogenic transplantation. We hypothesised that hTSCs, being partially reprogrammed in a state just prior to iPSC transition, could be isolated from any terminally differentiated cell type through transient reprogramming factor overexpression. Cytochemical staining of human deciduous tooth-derived dental pulp cells (HDDPCs) and human skin-derived fibroblasts following transfection with Yamanaka's factors demonstrated increased ALP activity, a stem cell marker, three weeks after transfection albeit in a small percentage of clones. Repeated transfections (≤3) led to more efficient iPSC generation, with HDDPCs exhibiting greater multipotentiality at two weeks post-transfection than the parental intact HDDPCs. These results indicated the utility of iPSC technology to isolate TSCs from HDDPCs and fibroblasts. Generally, a step-wise loss of pluripotential phenotypes in ESCs/iPSCs occurs during their differentiation process. Our present findings suggest that the reverse phenomenon can also occur upon repeated introduction of reprogramming factors into differentiated cells such as HDDPCs and fibroblasts.

    DOI： 10.1038/s41598-018-37291-2

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  • A Role for Prefrontal Cortical NMDA Receptors in Murine Alcohol-Heightened Aggression. Reviewed International journal

    Emily L Newman, Miho Terunuma, Tiffany L Wang, Nishani Hewage, Matthew B Bicakci, Stephen J Moss, Joseph F DeBold, Klaus A Miczek

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology   43 ( 6 )   1224 - 1234   2018.5

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

    DOI： 10.1038/npp.2017.253

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  • Diversity of structure and function of GABAB receptors: a complexity of GABAB-mediated signaling. Reviewed

    Miho Terunuma

    Proceedings of the Japan Academy. Series B, Physical and biological sciences   94 ( 10 )   390 - 411   2018

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    Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    γ-aminobutyric acid type B (GABAB) receptors are broadly expressed in the nervous system and play an important role in neuronal excitability. GABAB receptors are G protein-coupled receptors that mediate slow and prolonged inhibitory action, via activation of Gαi/o-type proteins. GABAB receptors mediate their inhibitory action through activating inwardly rectifying K+ channels, inactivating voltage-gated Ca2+ channels, and inhibiting adenylate cyclase. Functional GABAB receptors are obligate heterodimers formed by the co-assembly of R1 and R2 subunits. It is well established that GABAB receptors interact not only with G proteins and effectors but also with various proteins. This review summarizes the structure, subunit isoforms, and function of GABAB receptors, and discusses the complexity of GABAB receptors, including how receptors are localized in specific subcellular compartments, the mechanism regulating cell surface expression and mobility of the receptors, and the diversity of receptor signaling through receptor crosstalk and interacting proteins.

    DOI： 10.2183/pjab.94.026

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  • A Role for the GIRK3 Subunit in Methamphetamine-Induced Attenuation of GABAB Receptor-Activated GIRK Currents in VTA Dopamine Neurons. Reviewed International journal

    Michaelanne B Munoz, Claire L Padgett, Robert Rifkin, Miho Terunuma, Kevin Wickman, Candice Contet, Stephen J Moss, Paul A Slesinger

    The Journal of neuroscience : the official journal of the Society for Neuroscience   36 ( 11 )   3106 - 14   2016.3

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    DOI： 10.1523/JNEUROSCI.1327-15.2016

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  • Compromising the phosphodependent regulation of the GABAAR β3 subunit reproduces the core phenotypes of autism spectrum disorders. Reviewed International journal

    Thuy N Vien, Amit Modgil, Armen M Abramian, Rachel Jurd, Joshua Walker, Nicholas J Brandon, Miho Terunuma, Uwe Rudolph, Jamie Maguire, Paul A Davies, Stephen J Moss

    Proceedings of the National Academy of Sciences of the United States of America   112 ( 48 )   14805 - 10   2015.12

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    DOI： 10.1073/pnas.1514657112

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  • Purinergic receptor activation facilitates astrocytic GABAB receptor calcium signalling. Reviewed International journal

    Miho Terunuma, Philip G Haydon, Menelas N Pangalos, Stephen J Moss

    Neuropharmacology   88   74 - 81   2015.1

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.neuropharm.2014.09.015

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  • Glutamine synthetase stability and subcellular distribution in astrocytes are regulated by γ-aminobutyric type B receptors. Reviewed International journal

    Deborah Huyghe, Yasuko Nakamura, Miho Terunuma, Mathilde Faideau, Philip Haydon, Menelas N Pangalos, Stephen J Moss

    The Journal of biological chemistry   289 ( 42 )   28808 - 15   2014.10

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    DOI： 10.1074/jbc.M114.583534

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  • Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Reviewed International journal

    Armen M Abramian, Eydith Comenencia-Ortiz, Amit Modgil, Thuy N Vien, Yasuko Nakamura, Yvonne E Moore, Jamie L Maguire, Miho Terunuma, Paul A Davies, Stephen J Moss

    Proceedings of the National Academy of Sciences of the United States of America   111 ( 19 )   7132 - 7   2014.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.1403285111

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  • Postsynaptic GABAB receptor activity regulates excitatory neuronal architecture and spatial memory. Reviewed International journal

    Miho Terunuma, Raquel Revilla-Sanchez, Isabel M Quadros, Qiudong Deng, Tarek Z Deeb, Michael Lumb, Piotr Sicinski, Philip G Haydon, Menelas N Pangalos, Stephen J Moss

    The Journal of neuroscience : the official journal of the Society for Neuroscience   34 ( 3 )   804 - 16   2014.1

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    DOI： 10.1523/JNEUROSCI.3320-13.2013

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  • The ability of BDNF to modify neurogenesis and depressive-like behaviors is dependent upon phosphorylation of tyrosine residues 365/367 in the GABA(A)-receptor γ2 subunit. Reviewed International journal

    Mansi Vithlani, Rochelle M Hines, Ping Zhong, Miho Terunuma, Dustin J Hines, Raquel Revilla-Sanchez, Rachel Jurd, Phillip Haydon, Maribel Rios, Nicholas Brandon, Zhen Yan, Stephen J Moss

    The Journal of neuroscience : the official journal of the Society for Neuroscience   33 ( 39 )   15567 - 77   2013.9

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    DOI： 10.1523/JNEUROSCI.1845-13.2013

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  • Enhanced tonic inhibition influences the hypnotic and amnestic actions of the intravenous anesthetics etomidate and propofol. Reviewed International journal

    Karla Kretschmannova, Rochelle M Hines, Raquel Revilla-Sanchez, Miho Terunuma, Verena Tretter, Rachel Jurd, Max B Kelz, Stephen J Moss, Paul A Davies

    The Journal of neuroscience : the official journal of the Society for Neuroscience   33 ( 17 )   7264 - 73   2013.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1523/JNEUROSCI.5475-12.2013

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  • Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA. Reviewed International journal

    Claire L Padgett, Arnaud L Lalive, Kelly R Tan, Miho Terunuma, Michaelanne B Munoz, Menelas N Pangalos, José Martínez-Hernández, Masahiko Watanabe, Stephen J Moss, Rafael Luján, Christian Lüscher, Paul A Slesinger

    Neuron   73 ( 5 )   978 - 89   2012.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.neuron.2011.12.031

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  • Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation. Reviewed International journal

    Junko Odajima, Zachary P Wills, Yasmine M Ndassa, Miho Terunuma, Karla Kretschmannova, Tarek Z Deeb, Yan Geng, Sylwia Gawrzak, Isabel M Quadros, Jennifer Newman, Manjusri Das, Marie E Jecrois, Qunyan Yu, Na Li, Frederic Bienvenu, Stephen J Moss, Michael E Greenberg, Jarrod A Marto, Piotr Sicinski

    Developmental cell   21 ( 4 )   655 - 68   2011.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.devcel.2011.08.009

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  • Astrocytic activation of A1 receptors regulates the surface expression of NMDA receptors through a Src kinase dependent pathway. Reviewed International journal

    Qiudong Deng, Miho Terunuma, Tommaso Fellin, Stephen J Moss, Philip G Haydon

    Glia   59 ( 7 )   1084 - 93   2011.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/glia.21181

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  • The dynamic modulation of GABA(A) receptor trafficking and its role in regulating the plasticity of inhibitory synapses. Reviewed International journal

    Mansi Vithlani, Miho Terunuma, Stephen J Moss

    Physiological reviews   91 ( 3 )   1009 - 22   2011.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1152/physrev.00015.2010

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  • Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABAB receptors. Reviewed International journal

    Miho Terunuma, Karina J Vargas, Megan E Wilkins, Omar A Ramírez, Matías Jaureguiberry-Bravo, Menelas N Pangalos, Trevor G Smart, Stephen J Moss, Andrés Couve

    Proceedings of the National Academy of Sciences of the United States of America   107 ( 31 )   13918 - 23   2010.8

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    DOI： 10.1073/pnas.1000853107

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  • Functional modulation of GABAB receptors by protein kinases and receptor trafficking. Reviewed International journal

    Miho Terunuma, Menelas N Pangalos, Stephen J Moss

    Advances in pharmacology (San Diego, Calif.)   58   113 - 22   2010

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    GABA(B) receptors (GABA(B)R) are heterodimeric G protein-coupled receptors (GPCRs) that mediate slow and prolonged inhibitory signals in the central nervous system. The signaling of GPCRs is under stringent control and is subject to regulation by multiple posttranslational mechanisms. The beta-adrenergic receptor is a prototypic GPCR. Like most GPCRs, prolonged exposure of this receptor to agonist induces phosphorylation of multiple intracellular residues that is largely dependent upon the activity of G protein-coupled receptor kinases (GRKs). Phosphorylation terminates receptor-effector coupling and promotes both interaction with beta-arrestins and removal from the plasma membrane via clathrin-dependent endocytosis. Emerging evidence for GABA(B)Rs suggests that these GPCRs do not conform to this mode of regulation. Studies using both native and recombinant receptor preparations have demonstrated that GABA(B)Rs do not undergo agonist-induced internalization and are not GRK substrates. Moreover, whilst GABA(B)Rs undergo clathrin-dependent constitutive endocytosis, it is generally accepted that their rates of internalization are not modified by prolonged agonist exposure. Biochemical studies have revealed that GABA(B)Rs are phosphorylated on multiple residues within the cytoplasmic domains of both the R1 and R2 subunits by cAMP-dependent protein kinase and 5'AMP-dependent protein kinase (AMPK). Here we discuss the role that this phosphorylation plays in determining GABA(B)R effector coupling and their trafficking within the endocytic pathway and go on to evaluate the significance of GABA(B)R phosphorylation in controlling neuronal excitability under normal and pathological conditions.

    DOI： 10.1016/S1054-3589(10)58005-0

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  • Direct Interaction of GABA(B) Receptors with M-2 Muscarinic Receptors Enhances Muscarinic Signaling Reviewed

    Stephanie B. Boyer, Sinead M. Clancy, Miho Terunuma, Raquel Revilla-Sanchez, Steven M. Thomas, Stephen J. Moss, Paul A. Slesinger

    JOURNAL OF NEUROSCIENCE   29 ( 50 )   15796 - 15809   2009.12

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    DOI： 10.1523/JNEUROSCI.4103-09.2009

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  • Deficits in spatial memory correlate with modified gamma-aminobutyric acid type A receptor tyrosine phosphorylation in the hippocampus Reviewed

    Verena Tretter, Raquel Revilla-Sanchez, Catriona Houston, Miho Terunuma, Robbert Havekes, Cedrick Florian, Rachel Jurd, Mansi Vithlani, Guido Michels, Andres Couve, Werner Sieghart, Nicholas Brandon, Ted Abel, Trevor G. Smart, Stephen J. Moss

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   106 ( 47 )   20039 - 20044   2009.11

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    DOI： 10.1073/pnas.0908840106

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  • Endogenous nonneuronal modulators of synaptic transmission control cortical slow oscillations in vivo Reviewed

    Tommaso Fellin, Michael M. Halassa, Miho Terunuma, Francesca Succol, Hajime Takano, Marcos Frank, Stephen J. Moss, Philip G. Haydon

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   106 ( 35 )   15037 - 15042   2009.9

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    DOI： 10.1073/pnas.0906419106

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  • The Availability of Surface GABA(B) Receptors Is Independent of gamma-Aminobutyric Acid but Controlled by Glutamate in Central Neurons Reviewed

    Karina J. Vargas, Miho Terunuma, Judith A. Tello, Menelas N. Pangalos, Stephen J. Moss, Andres Couve

    JOURNAL OF BIOLOGICAL CHEMISTRY   283 ( 36 )   24641 - 24648   2008.9

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    DOI： 10.1074/jbc.M802419200

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  • Deficits in phosphorylation of GABA(A) receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus Reviewed

    Miho Terunuma, Jianwei Xu, Mansi Vithlani, Werner Sieghart, Josef Kittler, Menelas Pangalos, Philip G. Haydon, Douglas A. Coulter, Stephen J. Moss

    JOURNAL OF NEUROSCIENCE   28 ( 2 )   376 - 384   2008.1

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    DOI： 10.1523/JNEUROSCI.4346-07.2008

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  • Disrupted dentate granule cell chloride regulation enhances synaptic excitability during development of temporal lobe epilepsy Reviewed

    Hemal R. Pathak, Florian Weissinger, Miho Terunuma, Gregory C. Carlson, Fu-Chun Hsu, Stephen J. Moss, Douglas A. Coulter

    JOURNAL OF NEUROSCIENCE   27 ( 51 )   14012 - 14022   2007.12

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    DOI： 10.1523/JNEUROSCI.4390-07.2007

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  • mGluR5 stimulates gliotransmission in the nucleus accumbens Reviewed

    Marcello D'Ascenzo, Tommaso Fellin, Miho Terunuma, Raquel Revilla-Sanchez, David F. Meaney, Yves P. Auberson, Stephen J. Moss, Philip G. Haydon

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   104 ( 6 )   1995 - 2000   2007.2

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    DOI： 10.1073/pnas.0609408104

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  • Phospho-dependent functional modulation of GABA(B) receptors by the metabolic sensor AMP-dependent protein kinase Reviewed

    Nobuyuki Kuramoto, Megan E. Wilkins, Benjamin P. Fairfax, Raquel Revilla-Sanchez, Miho Terunuma, Keisuke Tamaki, Mika Iemata, Noel Warren, Andres Couve, Andrew Calver, Zsolt Horvath, Katie Freeman, David Carling, Lan Huang, Cathleen Gonzales, Edward Cooper, Trevor G. Smart, Menelas N. Pangalos, Stephen J. Moss

    NEURON   53 ( 2 )   233 - 247   2007.1

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    DOI： 10.1016/j.neuron.2006.12.015

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  • Identification of a Novel Signaling Molecule and Elucidation of Its Cellular Functions —Development of an Interface between Neuroscience and Oral Health Science— Reviewed

    Takashi Kanematsu, Akiko Mizokami, Miho Terunuma, Hiroshi Takeuchi, Masato Hirata

    Journal of Oral Biosciences   49 ( 4 )   244 - 258   2007

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    DOI： 10.2330/joralbiosci.49.244

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  • Protein phosphatase regulation by PRIP, a PLC-related catalytically inactive protein - Implications in the phospho-modulation of the GABA(A) receptor Reviewed

    Satoko Yanagihori, Miho Terunuma, Kiyoshi Koyano, Takashi Kanematsu, Sung Ho Ryu, Masato Hirata

    ADVANCES IN ENZYME REGULATION, VOL 46, PROCEEDINGS   46   203 - 222   2006

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    DOI： 10.1016/j.advenzreg.2006.01.006

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  • PRIP, a novel Ins(1,4,5)P-3 binding protein, functional significance in Ca2+ signaling and extension to neuroscience and beyond Reviewed

    T Kanematsu, H Takeuchi, M Terunuma, M Hirata

    MOLECULES AND CELLS   20 ( 3 )   305 - 314   2005.12

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  • Direct interaction of N-ethylmaleimide-sensitive factor with GABA(A) receptor beta subunits Reviewed

    H Goto, M Terunuma, T Kanematsua, Y Misumi, SJ Moss, M Hirata

    MOLECULAR AND CELLULAR NEUROSCIENCE   30 ( 2 )   197 - 206   2005.10

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    DOI： 10.1016/j.mcn.2005.07.006

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  • GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein Reviewed

    M Terunuma, IS Jang, SH Ha, JT Kittler, T Kanematsu, JN Jovanovic, KI Nakayama, N Akaike, SH Ryu, SJ Moss, M Hirata

    JOURNAL OF NEUROSCIENCE   24 ( 32 )   7074 - 7084   2004.8

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    DOI： 10.1523/JNEUROSCI.1323-04.2004

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  • The life cycle of the GABAA receptor and its regulating molecules Reviewed

    Takashi Kanematsu, Miho Terunuma, Hidefumi Goto, Akiko Kuratani, Masato Hirata

    Folia Pharmacologica Japonica   123 ( 2 )   105 - 112   2004

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  • Interaction of p130 with, and consequent inhibition of, the catalytic subunit of protein phosphatase 1 alpha Reviewed

    K Yoshimura, H Takeuchi, O Sato, K Hidaka, N Doira, M Terunuma, K Harada, Y Ogawa, Y Ito, T Kanematsu, M Hirata

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 21 )   17908 - 17913   2001.5

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    DOI： 10.1074/jbc.M009677200

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MISC

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Research Projects

  • Human deciduous dental pulp cells can help cure diabetes mellitus

    Grant number：25K02832

    2025.4 - 2028.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\18850000 （ Direct Cost: \14500000 、 Indirect Cost：\4350000 ）

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  • Unravel the function of median eminence perineuronal net by examining oral infectious disease

    Grant number：24K22181

    2024.6 - 2026.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Challenging Research (Exploratory)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\6500000 （ Direct Cost: \5000000 、 Indirect Cost：\1500000 ）

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  • チタン結晶構造制御とVUV照射による骨結合促進可能なインプラント表面開発

    Grant number：23K09292

    2023.4 - 2026.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    江口 香里, 秋葉 陽介, 魚島 勝美, 照沼 美穂

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Analysis of stress-protective neural circuits using an anxiolytic mouse model

    Grant number：23K06804

    2023.4 - 2026.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Development of a new bone augmentation method that enables long-term survival and long-term functional expression of transplanted cells by antioxidants

    Grant number：23K09272

    2023.4 - 2026.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

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  • Japan-Denmark joint research projects to identify the novel biological mechanism of anxiety

    Grant number：22KK0140

    2022.10 - 2026.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\20150000 （ Direct Cost: \15500000 、 Indirect Cost：\4650000 ）

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  • 末梢神経損傷により途切れた神経回路の人工シナプスコネクターによる感覚再生への挑戦

    Grant number：22K19615

    2022.6 - 2025.3

    System name：科学研究費助成事業

    Research category：挑戦的研究(萌芽)

    Awarding organization：日本学術振興会

    瀬尾 憲司, 前田 健康, 岸本 直隆, 照沼 美穂, 武内 恒成

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    Grant amount：\6370000 （ Direct Cost: \4900000 、 Indirect Cost：\1470000 ）

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  • 新規器官培養法による乳歯由来ヒトiPS細胞を経由したインスリン分泌細胞形成の誘導

    Grant number：22H03277

    2022.4 - 2025.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    齊藤 一誠, 佐藤 正宏, 野口 洋文, 照沼 美穂, 稲田 絵美, 薗村 貴弘

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    Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）

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  • Induction of insulin secreting cell via human iPS cells derived from deciduous teeth using a novel organ culture method

    Grant number：23K24535

    2022.4 - 2025.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）

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  • Impact of orofacial function on recovery from dysphagia caused by cerebrovascular disorders

    Grant number：21H03128

    2021.4 - 2024.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\17290000 （ Direct Cost: \13300000 、 Indirect Cost：\3990000 ）

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  • 規格化ナノ構造チタンによる接着蛋白質を介した組織形成制御可能な生体材料開発

    Grant number：21K09976

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    秋葉 陽介, 魚島 勝美, 照沼 美穂, 水野 潤, 泉 健次

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    デンタルインプラントにおいては、オッセオインテグレーションと呼ばれるチタンと骨の結合が認められる。インプラントの成功基準の一つにオッセオインテグレーションの確立、成立が上げられている。臨床的には、デンタルインプラント表面をエッチングやサンドブラストによって粗造化することによって、骨芽細胞の接着、分化、骨形成を促進することができるとされている。しかし、チタン表面の粗造化がどのような構造因子と、それを認識し得る、細胞のどのような機能で細胞分化を促進するのか、といった詳細なメカニズムについては、十分な理解が進んでしない。これまでの研究において、粗造化されたチタンにおける、骨骨芽細胞の分化促進機構を検証する際に使用されていた、研磨による平滑な無構造チタンとされているチタンにおいても、電子顕微鏡下では、研磨に伴う研磨痕が多く観察され、細胞、タンパク質レベルでは無構造ではなく極めて粗造な構造が認識されていると考えられる。しかし、チタンに規格化され、制御された構造をナノレベルで形成することは、技術的に困難である。これまでの研究においては、数百ナノメートルの非規格化構造や規格化構造であっても数マイクロのサイズでしか構造形成は実現できていない。本研究においては、表面粗さ数ナノメートルの無構造チタン基板を基本に、構造因子に影響されないチタン特異的接着タンパク質群を同定し、さらに粗面構造における接着タンパク質群を同定し、構造因子による骨芽細胞接着分化促進因子を同定するものである。規格化ナノ構造チタンにおいては規格化線状ナノ構造を形成したチタン基板上での細胞挙動、組織形成制御を確認するために、骨髄由来細胞を播種培養し、ナノ構造によって細胞活動が制御され得ることを確認済みである。また、無構造チタン基板上において、接着タンパク質群の回収及び解析を実施している。

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  • Identification of novel mechanism associating psychiatric disorders with periodontitis

    Grant number：21H03109

    2021.4 - 2024.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）

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  • Identification of novel mechanisms of alcohol-related dementia

    Grant number：18KK0258

    2018.10 - 2022.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Awarding organization：Japan Society for the Promotion of Science

    Terunuma Miho

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    Grant amount：\17940000 （ Direct Cost: \13800000 、 Indirect Cost：\4140000 ）

    Chronic alcohol consumption can lead to the development of hyperammonemia due to liver dysfunction. We identified that liver failure-associated hyperammonemia induces neuroinflammation which can be described by the increased number of reactive astrocytes in the brain. We also identified that ammonia stimulation induces the production of amyloid beta, a critical initiator that triggers the progression of Alzheimer’s disease. Using primary cultured astrocytes prepared from rat embryo, we found the mechanisms of amyloid beta production; ammonia enhances amyloid precursor protein (APP) endocytosis from the plasma membrane, induces transportation of APP to the endoplasmic reticulum, where two enzymes cleave APP to generate amyloid beta peptides. We reported these mechanisms as a novel mechanism driving Alzheimer’s disease.

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  • Biological reaction control using topography regulation of nanostructured titanium

    Grant number：18K09679

    2018.4 - 2021.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    AKIBA YOSUKE

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    In this study, we fabricated standardized and controlled periodic nanopatterns with nanosized surface roughness on titanium substrates and investigated their influence on bone marrow stromal cells. Cell proliferation assays revealed that the bare substrate with a 1.7 nm surface roughness showed lower hydrophilicity but higher proliferation ability than that with a 0.6 nm surface roughness. Further, with the latter substrate, directional cell growth was observed for line and groove patterns with a width of 100 nm and a height of 50 or 100 nm, but not for those with heights of 10 or 25 nm. With the smooth substrate, time-lapse microscopic analyses showed that more than 80% of the bone marrow cells on the line and groove pattern with a height of 100 nm grew and divided along the lines. As the nanosized grain structure controls the cell proliferation rate and the nanosized line and groove structure controls cell migration, division, and growth orientation.

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  • Identification of novel targets and concepts for cancer therapy

    Grant number：17K19748

    2017.6 - 2019.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Challenging Research (Exploratory)

    Awarding organization：Japan Society for the Promotion of Science

    Terunuma Miho, Amaya Yoshihiro, Harada Fumiko

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    Grant amount：\6370000 （ Direct Cost: \4900000 、 Indirect Cost：\1470000 ）

    We examined the anticancer effect of cellular energy sensor AMPK and inhibitory neurotransmitter receptor GABAB receptor and their functional crosstalk in oral cancer cells. We found that the structure of GABAB receptors are different from that of neuronal GABAB receptors and their activation did not induce anti-cancer effect. On the other hand, AMPK activation strongly suppressed the cancer proliferation. Therefore, in oral cancer, AMPK downstream signaling maybe a good target for novel drug development.

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  • Drug discovery for xerostomia treatment targeting oral mucosal epithelium-minor salivary gland units

    Grant number：17K12044

    2017.4 - 2022.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Kato Hiroko

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    Salivary secretion is enhanced by parasympathetically derived acetylcholine binding to muscarinic receptors. Currently, the indication of drugs for xerostomia is limited to specific cases such as Sjogren's syndrome and xerostomia after radiotherapy, however, an effective treatment with a broad indication is needed to reduce the risk of infections and other diseases caused by xerostomia. We hypothesized that the oral mucosal epithelial tissue contains a non-neurogenic cholinergic acetylcholine-producing system that is independent of neural tissue, and that acetylcholine secreted by the epithelial cells promotes salivary gland secretion of minor salivary glands.

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  • Regulatory mechanisms of appetite center

    Grant number：17H04372

    2017.4 - 2020.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Terunuma Miho

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    Grant amount：\17290000 （ Direct Cost: \13300000 、 Indirect Cost：\3990000 ）

    Metabolic syndrome is a conditions that is associated with diabetes and obesity. It is known that people with metabolic syndrome have altered hypothalamic function due to the dysfunction of astrocytes. This is known to lead to neuroinflammation which can be the cause of various neurodegenerative disorders.
    We have recently identified a molecule which regulate the expression of glutamine synthetase, a well known marker for astrocytes, that regulate the amount of glutamate, a major excitatory neurotransmitter in the brain. In this proposal, we examined if our molecule is involved in the regulation of glutamine synthetase expression in hypothalamic astrocytes by using cultured astrocytes and mice.

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  • GABA受容体の機能的構築に関わる新しい分子に関する研究

    Grant number：03J07823

    2003 - 2004

    System name：科学研究費助成事業

    Research category：特別研究員奨励費

    Awarding organization：日本学術振興会

    照沼 美穂

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    Grant amount：\1800000 （ Direct Cost: \1800000 ）

    GABA_A受容体β1-3サブユニット結合蛋白質PRIP-1がGABA_A受容体のリン酸化にどのような役割を果たしているかを解明するために以下の研究を行った。GABA_A受容体のリン酸化レベルを比較するために野生型、PRIP-1ノックアウト(PRIP-1^<-/->)マウスの海馬スライス標本を用いてPKAによるリン酸化を検討した。フォルスコリンで刺激したところ、PRIP-1^<-/->マウスでβ3サブユニットのS408/9のリン酸化が著明に減少していた。この原因を探るために、PKA活性を測定したところ違いは認められなかったが、PP1cαの活性がPRIP-1^<-/->マウスで約30%高かった。そこでPP1/PP2A活性阻害剤であるカリキュリンAやオカダ酸存在下にβ3サブユニットのリン酸化を検討したところ、PRIP-1^<-/->マウスでリン酸化レベルが回復した。また電気生理学的実験においても同様の結果が得られた。さらにPKAでリン酸化されたβ3サブユニットはPP1により著明に脱リン酸化されることも確認された。PRIP-1のリン酸化が脳細胞中でも起きるかを検討したところ、海馬、大脳皮質のいずれにおいてもリン酸化が観察され、さらにリン酸化によりPP1cαの結合が抑制された。PRIP-1のリン酸化部位を検索し、94番目のスレオニン(T94)、96番目のセリン(S96)がリン酸化残基であることを明らかにすると共にT94のリン酸化がPP1cαとの結合を制御していることも解明した。このことから、GABA_A受容体のPKAを介したリン酸化による機能的な調節にPRIP-1がPP1cαを受容体にリクルートする足場蛋白として関与していることをつきとめた。
    これらの結果はThe Journal of Neuroscience 24(32)20047074-7084に発表した。

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Teaching Experience

  • 基礎歯学ｺｰｽﾜｰｸ(国際連携基礎歯科学コース)

    2022
    -
    2023
    Institution name：新潟大学

  • 海外短期エクスターンシップ

    2022
    -
    2023
    Institution name：新潟大学

  • 神経生物学特論IIA

    2021
    Institution name：新潟大学

  • 基礎歯学ｺｰｽﾜｰｸ(ベーシック細胞生物学コースII)

    2021
    Institution name：新潟大学

  • 神経生物学特論IB

    2021
    Institution name：新潟大学

  • 神経生物学特論IA

    2021
    Institution name：新潟大学

  • 基礎歯学ｺｰｽﾜｰｸ(ベーシック細胞生物学コースI)

    2021
    Institution name：新潟大学

  • 神経生物学特論IIB

    2021
    Institution name：新潟大学

  • 短期海外派遣実習

    2021
    -
    2023
    Institution name：新潟大学

  • ネットワーク型先端歯学研究

    2021
    Institution name：新潟大学

  • 人体のしくみ

    2020
    Institution name：新潟大学

  • 早期臨床実習Ⅱ

    2018
    Institution name：新潟大学

  • 神経生物学特論ⅠA

    2018
    Institution name：新潟大学

  • 基礎生化学

    2017
    Institution name：新潟大学

  • 生化学実習

    2017
    Institution name：新潟大学

  • 基礎歯学コースワーク(ベーシック細胞生物学コースⅠ)

    2017
    -
    2018
    Institution name：新潟大学

  • 生化学Ⅱ

    2017
    Institution name：新潟大学

  • 神経生物学特論ⅡB

    2017
    Institution name：新潟大学

  • 神経生物学特論ⅡA

    2017
    Institution name：新潟大学

  • 生化学Ⅰ

    2017
    Institution name：新潟大学

  • 口腔生化学

    2016
    Institution name：新潟大学

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