Updated on 2024/12/14

写真a

 
FURUBE Eriko
 
Organization
School of Medicine Medical Course Basic Medicine Anatomy[Functional Anatomy and Neuroscience]
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Degree

  • Doctor (Philosophy) ( 2019.3   Kyoto Institute of Technology )

Research Interests

  • Demyelination

  • Oligodendrocyte

  • プロテアーゼ

  • 炎症

  • 脳室周囲器官

  • KLK6

  • KLK8

  • 神経新生

  • 血管新生

  • 神経幹細胞

Research Areas

  • Life Science / Anatomy

  • Life Science / Anatomy and histopathology of nervous system

Education

  • Kyoto Institute of Technology   Graduate School, Division of Engineering and Design Science   Applied Biology

    - 2019.3

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    Country: Japan

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  • Kyoto Institute of Technology   Applied Biology   Applied Biology

    - 2014.3

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    Country: Japan

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Research History

  • Asahikawa Medical College   Department of Functional Anatomy and Neuroscience.   Assistant Professor

    2020.4

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    Country:Japan

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  • 東邦大学医学部   解剖学講座微細形態学分野   助教

    2019.4 - 2020.3

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  • Toho University   School of Medicine, Faculty of Medicine

    2019.4 - 2020.3

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  • Kyoto Institute of Technology   Graduate School of Science and Technology

    2016.4 - 2019.3

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  • Kyoto Institute of Technology   Graduate School of Science and Technology

    2014.4 - 2016.3

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  • Kyoto Institute of Technology   School of Science and Technology

    2010.4 - 2014.3

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Professional Memberships

Papers

  • Neuronal regeneration in the area postrema of adult mouse medulla oblongata following glutamate-induced neuronal elimination. International journal

    Rena Fujii, Yuri Nambu, Nitin Sawant Shirikant, Eriko Furube, Mitsuhiro Morita, Ryoichi Yoshimura, Seiji Miyata

    Neuroscience   563   188 - 201   2024.11

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    Neural stem cells and/or progenitor cells (NSCs/NPCs) in the subventricular and subgranular zones of the adult mammal forebrain generate new neurons and are involved in partial repair after injury. Recently, NSCs/NPCs were identified in the area postrema (AP) of the medulla oblongata of the hindbrain. In this study, we used the properties of fenestrate capillaries to observe specific neuronal elimination in the AP of adult mice and investigated subsequent neuronal regeneration by neurogenesis. Subcutaneous administration of monosodium glutamate (MSG) induced prominent Fos expression in HuC/D+ neurons in the AP 2 h after administration. MSG administration caused a marked decrease in HuC/D+ neuronal density by neuronal death 3 to 21 days after administration, which recovered to the control level 35 days later. After MSG administration, the density of TUNEL+ dying neurons and phagocytic microglia surrounding or engulfing neurons increased. Within 7 days of MSG administration, the number of BrdU+ Sox2+ and BrdU+ Math1+ cells increased markedly, and at least the BrdU+ Math1+ cells similarly increased for the next following 7 days. A remarkable number of HuC/D+ neurons with BrdU+ nuclei were observed 35 days after MSG administration. This study reveals that neurogenesis occurs in the AP of adult mice, recovering and maintaining normal neuronal density after neuronal death.

    DOI: 10.1016/j.neuroscience.2024.11.009

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  • A high-fat diet influences neural stem and progenitor cell environment in the medulla of adult mice. International journal

    Eriko Furube, Masahiro Ohgidani, Yusuke Tanaka, Seiji Miyata, Shigetaka Yoshida

    Neuroscience   559   64 - 76   2024.8

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    It has been widely established that neural stem cells (NSCs) exist in the adult mammalian brain. The area postrema (AP) and the ependymal cell layer of the central canal (CC) in the medulla were recently identified as NSC niches. There are two types of NSCs: astrocyte-like cells in the AP and tanycyte-like cells in the CC. However, limited information is currently available on the characteristics and functional significance of these NSCs and their progeny in the AP and CC. The AP is a part of the dorsal vagal complex (DVC), together with the nucleus of the solitary tract (Sol) and the dorsal motor nucleus of the vagus (10 N). DVC is the primary site for the integration of visceral neuronal and hormonal cues that act to inhibit food intake. Therefore, we examined the effects of high-fat diet (HFD) on NSCs and progenitor cells in the AP and CC. Eight-week-old male mice were fed HFD for short (1 week) and long periods (4 weeks). To detect proliferating cells, mice consecutively received intraperitoneal injections of BrdU for 7 days. Brain sections were processed with immunohistochemistry using various cell markers and BrdU antibodies. Our data demonstrated that adult NSCs and neural progenitor cells (NPCs) in the medulla responded more strongly to short-term HFD than to long-term HFD. HFD increased astrocyte density in the Sol and 10 N, and increased microglial/macrophage density in the AP and Sol. Furthermore, long-term HFD induced mild inflammation in the medulla, suggesting that it affected the proliferation of NSCs and NPCs.

    DOI: 10.1016/j.neuroscience.2024.08.034

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  • Characterization of TRPM8-expressing neurons in the adult mouse hypothalamus. International journal

    Yousuke Tsuneoka, Taichi Nishikawa, Eriko Furube, Kaho Okamoto, Ryoichi Yoshimura, Hiromasa Funato, Seiji Miyata

    Neuroscience letters   814   137463 - 137463   2023.8

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    Transient receptor potential melastatin 8 (TRPM8) is a menthol receptor that detects cold temperatures and influences behaviors and autonomic functions under cold stimuli. Despite the well-documented peripheral roles of TRPM8, the evaluation of its central functions is still of great interest. The present study clarifies the nature of a subpopulation of TRPM8-expressing neurons in the adult mice. Combined in situ hybridization and immunohistochemistry revealed that TRPM8-expressing neurons are exclusively positive for glutamate decarboxylase 67 mRNA signals in the lateral septal nucleus (LS) and preoptic area (POA) but produced no positive signal for vesicular glutamate transporter 2. Double labeling immunohistochemistry showed the colocalization of TRPM8 with vesicular GABA transporter at axonal terminals. Immunohistochemistry further revealed that TRPM8-expressing neurons frequently expressed calbindin and calretinin in the LS, but not in the POA. TRPM8-expressing neurons in the POA expressed a prostaglandin E2 receptor, EP3, and neurotensin, whereas expression in the LS was minimal. These results indicate that hypothalamic TRPM8-expressing neurons are inhibitory GABAergic, while the expression profile of calcium-binding proteins, neurotensin, and EP3 differs between the POA and LS.

    DOI: 10.1016/j.neulet.2023.137463

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  • Systemic Inflammation Leads to Changes in the Intracellular Localization of KLK6 in Oligodendrocytes in Spinal Cord White Matter. International journal

    Eriko Furube, Masahiro Ohgidani, Shigetaka Yoshida

    Neurochemical research   2023.4

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    Axonal injury and demyelination occur in demyelinating diseases, such as multiple sclerosis, and the detachment of myelin from axons precedes its degradation. Paranodes are the areas at which each layer of the myelin sheath adheres tightly to axons. The destruction of nodal and paranodal structures during inflammation is an important pathophysiology of various neurological disorders. However, the underlying pathological changes in these structures remain unclear. Kallikrein 6 (KLK6), a serine protease produced by oligodendrocytes, is involved in demyelinating diseases. In the present study, we intraperitoneally injected mice with LPS for several days and examined changes in the localization of KLK6. Transient changes in the intracellular localization of KLK6 to paranodes in the spinal cord were observed during LPS-induced systemic inflammation. However, these changes were not detected in the upper part of brain white matter. LPS-induced changes were suppressed by minocycline, suggesting the involvement of microglia. Moreover, nodal lengths were elongated in LPS-treated wild-type mice, but not in LPS-treated KLK6-KO mice. These results demonstrate the potential involvement of KLK6 in the process of demyelination.

    DOI: 10.1007/s11064-023-03929-5

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  • Neurotoxicity Assessment System for Metals Using Mixed Cultures of Neural and Glial Cell Lines

    Ohgidani Masahiro, Furube Eriko, Tanaka Yusuke, Yoshida Shigetaka

    Alternatives to Animal Testing and Experimentation   28 ( 1 )   8 - 14   2023

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    Evaluations of the toxicity of hazardous substances in foods and other products are essential. Metals are severely neurotoxic to humans. To date, neurotoxicity has mainly been examined in animal experiments using rodents; however, the importance of using <i>in vitro</i> systems has recently been reported. Although the brain also contains glial cells, <i>in vitro</i> assessments of neurotoxicity have mainly been performed using neurons. Therefore, we established a high-throughput evaluation system by creating a mixed culture system of microglia, a type of glial cell, and neurons using BV2 and Neuro2A cells. The mixed culture showed changes in gene expression compared to the monoculture. Furthermore, in examinations of the toxicities of various metals, some exhibited different toxicities in the mixed culture from those in the single culture. These results suggest that the conventional evaluation system using single cultures is insufficient and also that the use of glial cells to accurately assess neurotoxicity may be necessary.

    DOI: 10.11232/aatex.28.8

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  • Neural stem cell phenotype of tanycyte-like ependymal cells in the circumventricular organs and central canal of adult mouse brain. Reviewed International journal

    Eriko Furube, Haruna Ishii, Yuri Nambu, Erkin Kurganov, Sumiharu Nagaoka, Mitsuhiro Morita, Seiji Miyata

    Scientific reports   10 ( 1 )   2826 - 2826   2020.2

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    Tanycyte is a subtype of ependymal cells which extend long radial processes to brain parenchyma. The present study showed that tanycyte-like ependymal cells in the organum vasculosum of the lamina terminalis, subfornical organ and central canal (CC) expressed neural stem cell (NSC) marker nestin, glial fibrillar acidic protein and sex determining region Y. Proliferation of these tanycyte-like ependymal cells was promoted by continuous intracerebroventricular infusion of fibroblast growth factor-2 and epidermal growth factor. Tanycytes-like ependymal cells in the CC are able to form self-renewing neurospheres and give rise mostly to new astrocytes and oligodendrocytes. Collagenase-induced small medullary hemorrhage increased proliferation of tanycyte-like ependymal cells in the CC. These results demonstrate that these tanycyte-like ependymal cells of the adult mouse brain are NSCs and suggest that they serve as a source for providing new neuronal lineage cells upon brain damage in the medulla oblongata.

    DOI: 10.1038/s41598-020-59629-5

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  • VEGF- and PDGF-dependent proliferation of oligodendrocyte progenitor cells in the medulla oblongata after LPC-induced focal demyelination. Reviewed International journal

    Daishi Hiratsuka, Erkin Kurganov, Eriko Furube, Mitsuhiro Morita, Seiji Miyata

    Journal of neuroimmunology   332   176 - 186   2019.7

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    The myelin sheath is critical in maintaining normal functions of the adult central nervous system (CNS) and the loss of the myelin sheath results in various neurological diseases. Although remyelination is the intrinsic repair system against demyelination that new myelin sheath is formed around axons in the adult CNS, little has been reported on remyelination system in the medulla oblongata. In the present study, we showed that the proliferation of oligodendrocyte progenitor cells (OPCs) was increased in the medulla oblongata by lysophosphatidylcholine (LPC)-induced focal demyelination, but that of NSCs was not changed. The inhibition of vascular endothelial growth factor (VEGF)- and platelet-derived growth factor (PDGF)-signaling suppressed the proliferation of OPCs by LPC-induced demyelination. Thus, the present study indicates that resident OPCs contribute to focal remyelination and VEGF and PDGF signaling is required for the proliferation of OPCs in the medulla oblongata of the adult mouse.

    DOI: 10.1016/j.jneuroim.2019.04.016

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  • Microglia are continuously activated in the circumventricular organs of mouse brain. Reviewed International journal

    Shohei Takagi, Eriko Furube, Yousuke Nakano, Mitsuhiro Morita, Seiji Miyata

    Journal of neuroimmunology   331   74 - 86   2019.6

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    Microglia are the primary resident immune cells of the brain parenchyma and transform into the amoeboid form in the "activated state" under pathological conditions from the ramified form in the "resting state" under physiologically healthy conditions. In the present study, we found that microglia in the circumventricular organs (CVOs) of adult mice displayed the amoeboid form with fewer branched cellular processes even under normal conditions; however, those in other brain regions showed the ramified form, which is characterized by well-branched and dendritic cellular processes. Moreover, microglia in the CVOs showed the strong protein expression of the M1 markers CD16/32 and CD86 and M2 markers CD206 and Ym1 without any pathological stimulation. Thus, the present results indicate that microglia in the CVOs of adult mice are morphologically and functionally activated under normal conditions, possibly due to the specialized features of the CVOs, namely, the entry of blood-derived molecules into parenchyma through fenestrated capillaries and the presence of neural stem cells.

    DOI: 10.1016/j.jneuroim.2017.10.008

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  • Oral gavage of capsaicin causes TRPV1-dependent acute hypothermia and TRPV1-independent long-lasting increase of locomotor activity in the mouse Reviewed

    H. Inagaki, E. Kurganov, Y. Pak, E. Furube, S. Miyata

    Physiology & Behavior   2019.4

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  • Remyelination in the medulla oblongata of adult mouse brain during experimental autoimmune encephalomyelitis. Reviewed International journal

    Daishi Hiratsuka, Eriko Furube, Katsutoshi Taguchi, Masaki Tanaka, Mitsuhiro Morita, Seiji Miyata

    Journal of neuroimmunology   319   41 - 54   2018.6

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    Experimental autoimmune encephalomyelitis (EAE) is primarily used as an animal model of autoimmune demyelinating disease, multiple sclerosis. In this study, we found the proliferative rate of oligodendrocyte progenitor cells (OPCs) in the medulla elevated twofold above control levels during EAE and new generation of mature oligodendrocytes was increased as well. Although astrocytes showed hypertrophic reactive phenotype, a new generation of them was rare. Astrocyte- and tanycyte-like neural stem cells (NSCs), multipotent NSCs, did not augment their low proliferative rate. Thus, the present study demonstrates that resident OPCs derived from NSCs contribute to remyelination in the medulla oblongata in EAE mice.

    DOI: 10.1016/j.jneuroim.2018.03.014

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  • Brain Region-dependent Heterogeneity and Dose-dependent Difference in Transient Microglia Population Increase during Lipopolysaccharide-induced Inflammation. Reviewed International journal

    Eriko Furube, Shintaro Kawai, Haruna Inagaki, Shohei Takagi, Seiji Miyata

    Scientific reports   8 ( 1 )   2203 - 2203   2018.2

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    Numerous studies have reported the importance of microglial activation in various pathological conditions, whereas little attention has been given to the point for dynamics of microglial population under infection-induced inflammation. In the present study, the single systemic stimulation of 100 μg/kg lipopolysaccharide (LPS) induced robust microglial proliferation only in the circumventricular organs (CVOs) and their neighboring brain regions. More than half of microglia similarly showed proliferative activity in the CVOs and their neighboring brain regions after 1 mg/kg LPS stimulation, while this stimulation expanded microglia-proliferating brain regions including the hypothalamus, medulla oblongata, and limbic system. Microglia proliferation resulted in a transient increase of microglial density, since their density almost returned to basal levels within 3 weeks. Divided microglia survived at the same rate as non-divided ones. Proliferating microglia frequently expressed a resident microglia marker Tmem119, indicating that increase of microglia density is due to the proliferation of resident microglia. Thus, the present study demonstrates that transient increase in microglia density depends on the brain region and dose of LPS during infection-induced inflammation and could provide a new insight on microglia functions in inflammation and pathogenesis of brain diseases.

    DOI: 10.1038/s41598-018-20643-3

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  • Structural Reconstruction of the Perivascular Space in the Adult Mouse Neurohypophysis During an Osmotic Stimulation Reviewed

    K. Nishikawa, E. Furube, S. Morita, N. Horii-Hayashi, M. Nishi, S. Miyata

    Journal of Neuroendocrinology   29 ( 2 )   2017.2

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    Oxytocin (OXT) and arginine vasopressin (AVP) neuropeptides in the neurohypophysis (NH) control lactation and body fluid homeostasis, respectively. Hypothalamic neurosecretory neurones project their axons from the supraoptic and paraventricular nuclei to the NH to make contact with the vascular surface and release OXT and AVP. The neurohypophysial vascular structure is unique because it has a wide perivascular space between the inner and outer basement membranes. However, the significance of this unique vascular structure remains unclear
    therefore, we aimed to determine the functional significance of the perivascular space and its activity-dependent changes during salt loading in adult mice. The results obtained revealed that pericytes were the main resident cells and defined the profile of the perivascular space. Moreover, pericytes sometimes extended their cellular processes or ‘perivascular protrusions’ into neurohypophysial parenchyma between axonal terminals. The vascular permeability of low-molecular-weight (LMW) molecules was higher at perivascular protrusions than at the smooth vascular surface. Axonal terminals containing OXT and AVP were more likely to localise at perivascular protrusions than at the smooth vascular surface. Chronic salt loading with 2% NaCl significantly induced prominent changes in the shape of pericytes and also increased the number of perivascular protrusions and the surface area of the perivascular space together with elevations in the vascular permeability of LMW molecules. Collectively, these results indicate that the perivascular space of the NH acts as the main diffusion route for OXT and AVP and, in addition, changes in the shape of pericytes and perivascular reconstruction occur in response to an increased demand for neuropeptide release.

    DOI: 10.1111/jne.12456

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  • TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation. Reviewed International journal

    Ayaka Yoshida, Eriko Furube, Tetsuya Mannari, Yasunori Takayama, Hiroki Kittaka, Makoto Tominaga, Seiji Miyata

    Scientific reports   6   26088 - 26088   2016.5

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    Transient receptor potential vanilloid receptor 1 (TRPV1) is a non-selective cation channel that is stimulated by heat (>43 °C), mechanical/osmotic stimuli, and low pH. The importance of TRPV1 in inflammatory responses has been demonstrated, whereas its participation in brains remains unclear. In the present study, the intracerebroventricular (icv) administration of the TRPV1 agonist resiniferatoxin (RTX) induced the activation of signal transducer and activator of transcription 3 (STAT3) in circumventricular organs (CVOs) and thermoregulation-associated brain regions with a similar patttern to the peripheral and icv administration of lipopolysaccharide (LPS). With the peripheral and icv LPS stimuli, STAT3 activation was significantly lower in Trpv1(-/-) mice than in Trpv1(+/+) mice. The icv administration of RTX induced transient hypothermia, whereas that of the TRPV1 antagonist capsazepine enhanced the magnitude and period of LPS-induced hyperthermia. These results indicate that TRPV1 is important for activating proinflammatory STAT3 signaling and thermoregulation-associated brain pathways in the brain.

    DOI: 10.1038/srep26088

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  • Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain. Reviewed International journal

    Shoko Morita, Eriko Furube, Tetsuya Mannari, Hiroaki Okuda, Kouko Tatsumi, Akio Wanaka, Seiji Miyata

    Cell and tissue research   363 ( 2 )   497 - 511   2016.2

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    Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB.

    DOI: 10.1007/s00441-015-2207-7

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  • Oligodendrogenesis in the fornix of adult mouse brain; the effect of LPS-induced inflammatory stimulation. Reviewed International journal

    Shohei Fukushima, Kazunori Nishikawa, Eriko Furube, Shiori Muneoka, Katsuhiko Ono, Hirohide Takebayashi, Seiji Miyata

    Brain research   1627   52 - 69   2015.11

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    Evidence have been accumulated that continuous oligodendrogenesis occurs in the adult mammalian brain. The fornix, projection and commissure pathway of hippocampal neurons, carries signals from the hippocampus to other parts of the brain and has critical role in memory and learning. However, basic characterization of adult oligodendrogenesis in this brain region is not well understood. In the present study, therefore, we aimed to examine the proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) and the effect of acute inflammatory stimulation on oligodendrogenesis in the fornix of adult mouse. We demonstrated the proliferation of OPCs and a new generation of mature oligodendrocytes by using bromodeoxyuridine and Ki67 immunohistochemistry. Oligodendrogenesis of adult fornix was also demonstrated by using oligodendrocyte transcription factor 2 transgenic mouse. A single systemic administration of lipopolysaccharide (LPS) attenuated proliferation of OPCs in the fornix together with reduced proliferation of hippocampal neural stem/progenitor cells. Time course analysis showed that a single administration of LPS attenuated the proliferation of OPCs during 24-48 h. On the other hand, consecutive administration of LPS did not suppress proliferation of OPCs. The treatment of LPS did not affect differentiation of OPCs into mature oligodendrocytes. Treatment of a microglia inhibitor minocycline significantly attenuated basal proliferation of OPCs under normal condition. In conclusion, the present study indicates that continuous oligodendrogenesis occurs and a single administration of LPS transiently attenuates proliferation of OPCs without changing differentiation in the fornix of the adult mouse brains.

    DOI: 10.1016/j.brainres.2015.09.011

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  • Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse. Reviewed International journal

    Eriko Furube, Mitsuhiro Morita, Seiji Miyata

    Cell and tissue research   362 ( 2 )   347 - 65   2015.11

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    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions.

    DOI: 10.1007/s00441-015-2201-0

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  • Robust increase of microglia proliferation in the fornix of hippocampal axonal pathway after a single LPS stimulation. Reviewed International journal

    Shohei Fukushima, Eriko Furube, Masanobu Itoh, Toshihiro Nakashima, Seiji Miyata

    Journal of neuroimmunology   285   31 - 40   2015.8

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    Microglia are resident immunocompetent cells having important roles in innate immunity in the brains. In the present study, we found that a single lipopolysaccharide (LPS) administration significantly increased microglial proliferation in the fornix and dentate gyrus (DG) but not the cerebral cortex and corpus callosum of adult mice. LPS-induced microglial proliferation was especially robust at the white matter of the fornix. The density of microglia increased in the fornix and DG for roughly one week and returned to basal levels at least 20days after a single LPS administration. Consecutive LPS administration did not induce such dramatic increase of microglial proliferation in the fornix. The inhibition of vascular endothelial growth factor signaling by AZD2171 largely suppressed LPS-induced increase of microglial proliferation in the fornix. In conclusion, the present study indicates that the hippocampal neuronal system has a higher proliferative microglial capability against LPS-induced inflammatory administration compared with other brain regions.

    DOI: 10.1016/j.jneuroim.2015.05.014

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  • Vascular endothelial growth factor-dependent angiogenesis and dynamic vascular plasticity in the sensory circumventricular organs of adult mouse brain. Reviewed International journal

    Shoko Morita, Eriko Furube, Tetsuya Mannari, Hiroaki Okuda, Kouko Tatsumi, Akio Wanaka, Seiji Miyata

    Cell and tissue research   359 ( 3 )   865 - 84   2015.3

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    The sensory circumventricular organs (CVOs), which comprise the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and the area postrema (AP), lack a typical blood-brain barrier (BBB) and monitor directly blood-derived information to regulate body fluid homeostasis, inflammation, feeding and vomiting. Until now, almost nothing has been documented about vascular features of the sensory CVOs except fenestration of vascular endothelial cells. We therefore examine whether continuous angiogenesis occurs in the sensory CVOs of adult mouse. The angiogenesis-inducing factor vascular endothelial growth factor-A (VEGF-A) and the VEGF-A-regulating transcription factor hypoxia-inducible factor-1α were highly expressed in neurons of the OVLT and SFO and in both neurons and astrocytes of the AP. Expression of the pericyte-regulating factor platelet-derived growth factor B was high in astrocytes of the sensory CVOs. Immunohistochemistry of bromodeoxyuridine and Ki-67, a nuclear protein that is associated with cellular proliferation, revealed active proliferation of endothelial cells. Moreover, immunohistochemistry of caspase-3 and the basement membrane marker laminin showed the presence of apoptosis and sprouting of endothelial cells, respectively. Treatment with the VEGF receptor-associated tyrosine kinase inhibitor AZD2171 significantly reduced proliferation and filopodia sprouting of endothelial cells, as well as the area and diameter of microvessels. The mitotic inhibitor cytosine-b-D-arabinofuranoside reduced proliferation of endothelial cells and the vascular permeability of blood-derived low-molecular-weight molecules without changing vascular area and microvessel diameter. Thus, our data indicate that continuous angiogenesis is dependent on VEGF signaling and responsible for the dynamic plasticity of vascular structure and permeability.

    DOI: 10.1007/s00441-014-2080-9

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  • Astrocytic TLR4 expression and LPS-induced nuclear translocation of STAT3 in the sensory circumventricular organs of adult mouse brain. Reviewed International journal

    Yousuke Nakano, Eriko Furube, Shoko Morita, Akio Wanaka, Toshihiro Nakashima, Seiji Miyata

    Journal of neuroimmunology   278   144 - 58   2015.1

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    The sensory circumventricular organs (CVOs) comprise the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP) and lack the blood-brain barrier. The expression of Toll-like receptor 4 (TLR4) was seen at astrocytes throughout the sensory CVOs and at microglia in the AP and solitary nucleus around the central canal. The peripheral and central administration of lipopolysaccharide induced a similar pattern of nuclear translocation of STAT3. A microglia inhibitor minocycline largely suppressed lipopolysaccharide-induced astrocytic nuclear translocation of STAT3 in the OVLT and AP, but its effect was less in the SFO.

    DOI: 10.1016/j.jneuroim.2014.12.013

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  • Antidepressant-induced vascular dynamics in the hippocampus of adult mouse brain. Reviewed International journal

    Tetsuya Mannari, Hayato Sawa, Eriko Furube, Shohei Fukushima, Kazunori Nishikawa, Toshihiro Nakashimna, Seiji Miyata

    Cell and tissue research   358 ( 1 )   43 - 55   2014.10

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    New neurons are continuously added to hippocampal circuitry involved with spatial learning and memory throughout life. These new neurons originate from neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). Recent studies indicate that vascular reconstruction is closely connected with neurogenesis, but little is known about its mechanism. We have examined vascular reconstruction in the hippocampus of adult mouse brain after the administration of the antidepressant fluoxetine, a potent inducer of hippocampal neurogenesis. The immunohistochemistry of laminin and CD31 showed that filopodia of endothelial cells sprouted from existing thick microvessels and often formed a bridge between two thick microvessels. These filopodia were frequently seen at the molecular layer and dentate hilus of the DG, the stratum lacunosum-moleculare of the CA1, and the stratum oriens of the CA3. The filopodia were exclusively localized along cellular processes of astrocytes, but such intimate association was not seen with cell bodies and processes of NSPCs. The administration of fluoxetine significantly increased vascular density by enlarging the luminal size of microvessels and eliminating the filopodia of endothelial cells in the molecular layer and dentate hilus. Treatment with fluoxetine increased the number of proliferating NSPCs in the granule cell layer and dentate hilus, and that of endothelial cells in the granule cell layer. Thus, antidepressant-induced vascular dynamics in the DG are possibly attributable to the alteration of the luminal size of microvessels rather than to proliferation of endothelial cells.

    DOI: 10.1007/s00441-014-1933-6

    PubMed

    J-GLOBAL

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  • VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice. Reviewed International journal

    Eriko Furube, Tetsuya Mannari, Shoko Morita, Kazunori Nishikawa, Ayaka Yoshida, Masanobu Itoh, Seiji Miyata

    The Journal of endocrinology   222 ( 1 )   161 - 79   2014.7

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    Hypothalamo-neurohypophysial system (HNS) releases arginine vasopressin (AVP) and oxytocin (OXT) from axonal terminals of the neurohypophysis (NH) into blood circulation for controlling body fluid homeostasis and lactation. Chronic osmotic and suckling stimulations have been shown to cause neurovascular and neuroglial reconstruction in the NH of adult mammals and no study has been reported for vascular dynamics. The aim of this study was to elucidate the occurrence of continuous angiogenesis and growth factor-dependent neurovascular reconstruction in the NH of adult mice. Active proliferation of endothelial cells and oligodendrocyte progenitor cells (OPCs) was observed using the immunohistochemistry of bromodeoxyuridine and Ki-67. Vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2 (KDR)) were highly expressed at pituicytes and endothelial cells respectively. Moreover, prominent expression of platelet-derived growth factor B (PDGFB) and PDGF receptor beta was observed at OXT-containing axonal terminals and pericytes respectively. Administration of the selective tyrosine kinase inhibitor AZD2171 for VEGFRs and STI571 for PDGFRs significantly decreased proliferation of endothelial cells and OPCs. Moreover, AZD2171 treatment decreased vascular density by facilitating apoptosis of endothelial cells and the withdrawal of its treatment led to remarkable rebound proliferation of endothelial cells, so that vascular density rapidly returned to normal levels. AZD2171 decreased the density of both AVP- and OXT-containing axonal terminals, whereas STI571 selectively decreased the density of AVP-containing ones. Thus, this study demonstrates that the signaling pathways of VEGF and PDGF are crucial mediators for determining proliferation of endothelial cells and OPCs and the density of AVP- and OXT-containing axonal terminals in the HNS.

    DOI: 10.1530/JOE-14-0075

    PubMed

    J-GLOBAL

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  • Astrocytic TRPV1 ion channels detect blood-borne signals in the sensory circumventricular organs of adult mouse brains. Reviewed International journal

    Tetsuya Mannari, Shoko Morita, Eriko Furube, Makoto Tominaga, Seiji Miyata

    Glia   61 ( 6 )   957 - 71   2013.6

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    The circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP) sense a variety of blood-borne molecules because they lack typical blood-brain barrier. Though a few signaling pathways are known, it is not known how endogenous ligands for transient receptor potential vanilloid receptor 1 ion channel (TRPV1) are sensed in the CVOs. In this study, we aimed to examine whether or not astrocytic TRPV1 senses directly blood-borne molecules in the OVLT, SFO, and AP of adult mice. The reverse transcription-polymerase chain reaction and Western analysis revealed the expression of TRPV1 in the CVOs. Confocal microscopic immunohistochemistry further showed that TRPV1 was localized prominently at thick cellular processes of astrocytes rather than fine cellular processes and cell bodies. TRPV1-expressing cellular processes of astrocytes surrounded the vasculature to constitute dense networks. The expression of TRPV1 was also found at neuronal dendrites but not somata in the CVOs. The intravenous administration of a TRPV1 agonist resiniferatoxin (RTX) prominently induced Fos expression at astrocytes in the OVLT, SFO, and AP and neurons in adjacent related nuclei of the median preoptic nuclei (MnPO) and nucleus of the solitary tract (Sol) of wild-type but not TRPV1-knockout mice. The intracerebroventricular infusion of RTX induced Fos expression at both astrocytes and neurons in the CVOs, MnPO, and Sol. Thus, this study demonstrates that blood-borne molecules are sensed directly by astrocytic TRPV1 of the CVOs in adult mammalians.

    DOI: 10.1002/glia.22488

    PubMed

    J-GLOBAL

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  • Behavioral analysis of relaxin-3 deficient mice. Reviewed International journal

    Masaki Tanaka, Eriko Furube, Miku Aoki, Yoshihisa Watanabe

    Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia   118 ( 1 Suppl )   56 - 9   2013

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    Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus of the pons, projecting axons to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. We generated relaxin-3 gene knockout (KO) mice and examined them using a battery of behavioral tests of sensory/motor functions and emotion-related behaviors. Relaxin-3 KO mice exhibited normal growth and appearance. There was no difference in bodyweight among genotypes in both normal and high fat diet feeding. In addition, there were no significant differences between wild-type and KO mice in social interaction, depression-like behavior, and short memory test. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the open field test. Taken together, these results indicate that relaxin-3 KO mice exhibit mild anxiolytic characteristics relative to wild-type mice, suggesting that this peptide is involved in anxiety-related behavior.

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MISC

  • 脳室面は成体における神経幹細胞のニッチである

    古部瑛莉子, 宮田清司

    Bio Clinica   34 ( 13 )   70 - 74   2019.11

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    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher:北隆館  

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  • 脳室面は成体における神経幹細胞のニッチである

    古部 瑛莉子, 宮田 清司

    BIO Clinica   34 ( 13 )   1356 - 1360   2019.11

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    Language:Japanese   Publisher:(株)北隆館  

    成体の脳には、神経幹細胞が存在していないと長年考えられ、新しい神経細胞やグリア細胞の供給はないと思われてきた。しかし、約20年前に海馬と側脳室下帯に神経幹細胞が存在することが報告され、ヒトにおいてもその存在が証明されている。神経幹細胞は、脳の機能維持だけでなく損傷後の組織修復に関わることが知られている。近年、筆者らは視床下部や延髄を含む脳幹においても神経幹細胞の存在を証明した。この事実は、今まで考えられてたよりも脳の幅広い部位に新たな細胞の新生が生じていることを示している。本稿では、新たに発見された脳室周囲器官と中心管における神経幹細胞について、筆者らのデータを中心に概説する。(著者抄録)

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  • 末梢炎症刺激によるマウス脳室周囲器官のミクログリア増殖

    古部 瑛莉子, 宮田 清司

    日本組織細胞化学会総会・学術集会講演プログラム・予稿集   56回   76 - 76   2015.10

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  • 感知系脳室周囲器官のタニサイト様神経幹細胞

    古部 瑛莉子, 森田 光洋, 宮田 清司

    日本内分泌学会雑誌   91 ( 2 )   517 - 517   2015.9

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  • VEGFとPDGFに依存した下垂体後葉の血管新生と終末-血管のダイナミクス

    古部 瑛莉子, 萬成 哲也, 森田 晶子, 宮田 清司

    日本内分泌学会雑誌   90 ( 2 )   607 - 607   2014.9

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  • Active participation of vasculature in immune-to-brain communication in the sensory circumventricular organs

    S. Morita, K. Nakahara, E. Furube, K. Tatsumi, H. Okuda, A. Hourai, S. Miyata, A. Wanaka

    JOURNAL OF NEUROCHEMISTRY   130   49 - 49   2014.8

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY-BLACKWELL  

    Web of Science

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Presentations

  • Effects of high-fat diet intake on proliferation of neural stem/progenitor cells in the area postrema.

    Furube Eriko, Ohgidani Masahiro, Tanaka Yusuke, Shigetaka Yoshida

    第129回日本解剖学会総会・全国学術集会 

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    Event date: 2024.3

    Language:English   Presentation type:Oral presentation (general)  

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  • Analysis the time-dependent changes in KLK6 expression and its effects on motor function in the mouse tMCAO model.

    Eriko Furube

    第27回グリア研究会 

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    Event date: 2023.12

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • マウス中大脳動脈閉塞再灌流モデルにおける KLK6 の発現変化と虚血脳損傷に及ぼす影響

    古部瑛莉子, 扇谷昌宏, 田中佑典, 吉田成孝

    日本解剖学会 第69回 東北・北海道連合支部学術集会 

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    Event date: 2023.9

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Systemic inflammation leads to changes in the intracellular localization of KLK6 in oligodendrocytes in spinal cord

    Furube Eriko, Ohgidani Masahiro, Tanaka Yusuke, Shigetaka Yoshida

    第64回日本神経病理学会総会学術研究会/第66回日本神経化学会大会 合同大会 

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    Event date: 2023.7

    Language:English   Presentation type:Poster presentation  

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  • スクロース飲水および高脂肪食摂取が最後野神経幹/前駆細胞の増殖に与える影響

    古部瑛莉子, 扇谷昌宏, 吉田成孝

    第128回日本解剖学会総会・全国学術集会 

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    Event date: 2023.3

    Language:English   Presentation type:Poster presentation  

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  • Changes in the intracellular localization of Klk6 to paranodes in oligodendrocytes of the central nervous system during LPS-induced systemic inflammation

    Eriko Furube

    グリア研究会  グリア研究会/田辺三菱製薬株式会社

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    Event date: 2022.12

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • LPS誘発全身炎症中の中枢神経系のオリゴデンドロサイトにおけるKlk6のパラノードへの細胞内局在変化

    古部瑛莉子, 扇谷昌宏, 吉田成孝

    日本解剖学会第 68 回東北・北海道連合支部学術集会 

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    Event date: 2022.9

    Language:English   Presentation type:Oral presentation (general)  

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  • 最後野神経幹細胞に対する摂食の影響

    古部瑛莉子

    第127回日本解剖学会総会・全国学術集会  佐藤 真(大阪大学大学院医学系研究科/連合小児発達学研究科・医学部)

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    Event date: 2022.3 - 2022.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:オンライン  

    成体哺乳類の脳で、神経幹細胞が存在し、神経新生が起こる場所として最も研究されているのは海馬歯状回と側脳室下帯であり、海馬歯状回は記憶の形成、側脳室下帯は嗅覚依存行動に関与することが知られる。近年、これらの部位以外に脳室周囲器官である延髄最後野にも神経幹細胞が存在することが示されている。しかし最後野の神経幹細胞についての特徴や機能についての報告はほとんどない。本研究では、Nestin-CreERT2/CAG-CATloxP/loxP-EGFPマウスおよびBrdUを用いた免疫組織化学の結果から、最後野にはNestin陽性のアストロサイト様神経幹細胞と、ependymal cell layer に存在し、脳実質側に伸びる長い突起を有したタニサイト様神経幹細胞の2種類の神経幹細胞が存在することが明らかにした。分化について調べたところ、脳室周囲器官だけでなく、孤束核や迷走神経核、舌下神経核などの隣接した脳部位にも細胞を供給しており、その多くはオリゴデンドロサイトであることが判明した。最後野は嘔吐中枢として知られる領域であり、その周辺には孤束核、迷走神経核、舌下神経核などの摂食に関連する脳領域が存在する。そこで、最後野の神経幹細胞が高脂肪食摂取およびスクロース飲水によりどのような影響を受けるのかを検討した。

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  • LPSによる全身炎症モデルおよび外傷性脊髄損傷モデルを用いた脱髄関連プロテアーゼKLK6の細胞内局在変化

    古部瑛莉子

    グリア研究会  グリア研究会/田辺三菱製薬株式会社

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    Event date: 2021.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:オンライン  

    Oligodendrocytes (OLs) support signal transmission in the central nervous system by synthesizing myelin and enwrapping axons. Main functions of myelin are to cluster sodium channels into the nodes of Ranvier and to reduce ion leakage, enables saltatory conduction.
    Kallikrein 6 (KLK6), a serine protease is mainly produced by mature OLs in the CNS. KLK6 is upregulated in OLs after spinal cord injury (SCI) and in experimental autoimmune encephalomyelitis. High expression levels of KLK6 results in loss of processes in differentiated OLs in vitro. However, how changes in KLK6 expression level affect axon-myelin interactions during inflammation is not well understood.
    In the present study, we examined localization and characterization of KLK6 of OLs in lipopolysaccharide (LPS)-induced systemic inflammation model and traumatic spinal cord injury. LPS led to microglial activation in the anterior commissure(aca), corpus callosum (cc), ventral hippocampal commissure(vhc), fimbria of the hippocampus (fi), spinal trigeminal tract (sp5), pyramidal tract(py) and spinal cord white matter. Moreover, LPS increased KLK6- immunopositive structures in the sp5 and spinal cord white matter but not in the aca, cc, vhc, fi and py. We found that strong KLK6 immunoreactivity in paranodes. Both LPS-induced microglial activation and increase of KLK6-immunopositive structures were suppressed by minocycline, an anti-inflammatory drug that inhibits microglia /macrophage activation, in the spinal cord white matter. Localization change of KLK6 was also observed in the mouse model of SCI.

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  • 感知系脳室周囲器官神経幹細胞の機能的役割の解明

    古部瑛莉子

    日本解剖学会 第67回東北・北海道連合支部学術集会  東北大学医学部 ・ 医学系研究科 器官解剖学分野 大和田 祐二

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    Event date: 2021.9

    Language:English   Presentation type:Oral presentation (general)  

    Venue:オンライン  

    成体哺乳類の脳で、神経幹細胞が存在し、神経新生が起こる場所として最も研究されているのは海馬歯状回と側脳室下帯であり、海馬歯状回は記憶の形成、側脳室下帯は嗅覚依存行動に関与することが知られる。近年、これらの部位以外に脳室周囲器官にも神経幹細胞が存在することが示されている。しかし、感知系脳室周囲器官である終板器官、脳弓下器官、最後野の神経幹細胞についての特徴や意義についての報告はほとんどない。本研究では、Nestin-CreERT2/CAG-CATloxP/loxP-EGFPマウスおよびBrdUを用いた免疫組織化学の結果から、感知系脳室周囲器官にはNestin陽性のアストロサイト様神経幹細胞と、ependymal cell layer に存在し、脳実質側に伸びる長い突起を有したタニサイト様神経幹細胞の2種類の神経幹細胞が存在することが明らかにした。アストロサイト様神経幹細胞はほぼすべてがGFAP陽性であったが、タニサイト様神経幹細胞にはGFAP陽性のものとそうでないものが存在していたことから、さらに複数のタイプに分けることができると考えられる。分化について調べたところ、脳室周囲器官だけでなく、隣接した脳部位にも細胞を供給しており、その多くはオリゴデンドロサイトであることが判明した。神経幹細胞の機能的役割を調べるため、マウスに50w/v%スクロース水を3週間飲水させたところ最後野神経幹細胞および前駆細胞の増殖が促進されており、摂食またはエネルギー代謝の制御に関わる可能性が示唆された。

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  • Changes in intracellular localization of kallikrein 6 in lipopolysaccharide-induced systemic inflammation model and traumatic spinal cord injury

    Eriko Furube, Soshi Kanemoto, Hitomi Nakazawa, Shigetaka Yoshida

    第44回日本神経科学大会/第1回CJK国際会議  尾藤 晴彦(東京大学大学院医学系研究科)

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    Event date: 2021.7

    Language:English   Presentation type:Poster presentation  

    Venue:神戸コンベンションセンター/Hybrid開催  

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Research Projects

  • 成体延髄神経幹細胞ニッチに着目した摂食抑制メカニズムの解明

    2023.4 - 2025.3

    若手研究

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    飽食の時代である現在、肥満や糖尿病などの摂食に起因した生活習慣病の罹患者は増え続け、大きな問題となっている。脳室周囲器官の最後野(AP)は血液脳関門のない特徴的な脳領域であることが知られている。申請者はこれまで、APでは成体でも細胞新生が盛んに生じ、周囲の孤束核や舌下神経核等の摂食に関わる脳領域に細胞供給をしていることを見出してきた。さらに高脂肪食摂取時にAPにおいて神経幹細胞、前駆細胞が活発に増殖し、神経細胞新生やオリゴデンドロサイトをメインとしたグリア細胞新生が生じていることを発見した。しかし、高脂肪食摂取により新生した神経細胞が組み込まれる神経回路や、摂食行動にどのような変化を及ぼしているのかはまだ分かっていない。そこで本研究では、高脂肪食摂取時に焦点を当て、AP神経幹細胞の摂食に対する機能的役割の解明を目指す。AP神経幹細胞による摂食制御機構が判明すれば、社会的に大きな問題である肥満や糖尿病などの生活習慣病に対する血液脳関門を考慮しない薬剤の開発に繋がることも期待される。

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  • Elucidation of the functional role of neural stem cells in the area postrema in the regulation of feeding behavior

    Grant number:21K15177  2021.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

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    Grant amount:\4,550,000 ( Direct Cost: \3,500,000 、 Indirect Cost:\1,050,000 )

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  • 外傷性脊髄損傷の病態解析およびカリクレイン関連プロテアーゼ6に焦点をあてた治療法開発

    2021.4 - 2022.3

    公益財団法人 秋山記念生命科学振興財団  2021年度研究助成 

    古部瑛莉子

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  • 成体感知系脳室周囲器官神経幹細胞の摂食・エネルギー代謝への役割

    2021.4 - 2022.3

    公益財団法人 寿原記念財団 第35回研究助成 

    古部瑛莉子

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  • 敗血症モデルを用いたニューロプシンの機能解析

    2020.10 - 2021.10

    公益財団法人 金原一郎記念医学医療振興財団  第35回基礎医学医療研究助成金 

    古部瑛莉子

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  • Elucidation of brain regions and cell types in the regulation of sleep

    Grant number:19K23783  2019.8 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up  Grant-in-Aid for Research Activity start-up

    Furube Eriko

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    Grant amount:\2,860,000 ( Direct Cost: \2,200,000 、 Indirect Cost:\660,000 )

    In this study, we investigated the effect of SIK3 on causing inflammatory sleep / wake abnormalities in mice by intracerebroventricular(icv) administration of LPS, which constitutes the cell wall of Gram-negative bacteria.
    As a result of icv administration of LPS to wild-type mice, wake time decreased, NREM delta, which is an index of sleep depth, increased, NREM sleep time increased, and REM sleep decreased significantly. On the other hand, these changes were diminished in transgenic mice with enhanced SIK3 phosphorylation capacity. Immunohistochemical examination revealed that NeuN-positive neurons expressed SIK3. In addition, as a result of icv administration of LPS , it was found that HDAC4 nuclear translocation in neurons in the lateral hypothalamic area was suppressed in wild-type mice.

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  • Neural stem cell in the sensory circumventricular organs

    Grant number:16J10225  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows  Grant-in-Aid for JSPS Fellows

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2,800,000 ( Direct Cost: \2,800,000 )

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  • 下垂体後葉の血管系ネットワーク再構築による神経分泌調節

    2015.4 - 2016.3

    公益財団法人・日本科学協会  笹川科学研究助成 

    古部 瑛莉子

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    Authorship:Principal investigator  Grant type:Competitive

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  • 第35回寿原記念財団研究助成金

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    Grant type:Competitive

    Grant amount:\1,000,000

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  • LPSによる全身炎症および外傷性脊髄損傷モデルを用いた脱髄関連プロテアーゼKLK6の細胞内局在変化

    民間学術研究振興費補助金 

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