2023/02/05 更新

写真a

ヨシオカ ノゾム
吉岡 望
YOSHIOKA Nozomu
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 生体機能調節医学専攻 感覚統合医学 助教
職名
助教
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外部リンク

学位

  • 博士(理学) ( 2012年3月   首都大学東京 )

研究キーワード

  • 末梢神経系

  • 意思決定

  • ニューロパチー

  • 運動回路

  • 不随意運動

  • 反応性アストロサイト

  • ウイルスベクター

  • 皮質線条体路

  • 遺伝子改変マウス

  • 神経再生

  • 神経発生

  • コンドロイチン硫酸プロテオグリカン

  • ジストニア

研究分野

  • ライフサイエンス / 解剖学

経歴

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 感覚統合医学   助教

    2022年4月 - 現在

  • 新潟大学   教育研究院 医歯学系 医学系列   助教

    2022年4月 - 現在

  • 新潟大学   研究推進機構 超域学術院   助教

    2018年4月 - 2022年3月

  • 新潟大学   研究推進機構 超域学術院   特任助教

    2017年1月 - 2018年3月

所属学協会

 

論文

  • Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy. 査読 国際誌

    Youichi Shinozaki, Alex Leung, Kazuhiko Namekata, Sei Saitoh, Huy Bang Nguyen, Akiko Takeda, Yosuke Danjo, Yosuke M Morizawa, Eiji Shigetomi, Fumikazu Sano, Nozomu Yoshioka, Hirohide Takebayashi, Nobuhiko Ohno, Takahiro Segawa, Kunio Miyake, Kenji Kashiwagi, Takayuki Harada, Shin-Ichi Ohnuma, Schuichi Koizumi

    Science advances   8 ( 44 )   eabq1081   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Astrocyte abnormalities have received great attention for their association with various diseases in the brain but not so much in the eye. Recent independent genome-wide association studies of glaucoma, optic neuropathy characterized by retinal ganglion cell (RGC) degeneration, and vision loss found that single-nucleotide polymorphisms near the ABCA1 locus were common risk factors. Here, we show that Abca1 loss in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice. ABCA1 was highly expressed in retinal astrocytes in mice. Thus, we generated macroglia-specific Abca1-deficient mice (Glia-KO) and found that aged Glia-KO mice had RGC degeneration and ocular dysfunction without affected intraocular pressure, a conventional risk factor for glaucoma. Single-cell RNA sequencing revealed that Abca1 deficiency in aged Glia-KO mice caused astrocyte-triggered inflammation and increased the susceptibility of certain RGC clusters to excitotoxicity. Together, astrocytes play a pivotal role in eye diseases, and loss of ABCA1 in astrocytes causes glaucoma-like neuropathy.

    DOI: 10.1126/sciadv.abq1081

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  • Isoform-specific mutation in Dystonin-b gene causes late-onset protein aggregate myopathy and cardiomyopathy 査読 国際誌

    Nozomu Yoshioka, Masayuki Kurose, Masato Yano, Dang Minh Tran, Shujiro Okuda, Yukiko Mori-Ochiai, Masao Horie, Toshihiro Nagai, Ichizo Nishino, Shinsuke Shibata, Hirohide Takebayashi

    eLife   11   2022年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:eLife Sciences Publications, Ltd  

    Dystonin (DST), which encodes cytoskeletal linker proteins, expresses three tissue-selective isoforms: neural DST-a, muscular DST-b, and epithelial DST-e. DST mutations cause different disorders, including hereditary sensory and autonomic neuropathy 6 (HSAN-VI) and epidermolysis bullosa simplex; however, etiology of the muscle phenotype in DST-related diseases has been unclear. Because DST-b contains all of the DST-a-encoding exons, known HSAN-VI mutations could affect both DST-a and DST-b isoforms. To investigate the specific function of DST-b in striated muscles, we generated a Dst-b-specific mutant mouse model harboring a nonsense mutation. Dst-b mutant mice exhibited late-onset protein aggregate myopathy and cardiomyopathy without neuropathy. We observed desmin aggregation, focal myofibrillar dissolution, and mitochondrial accumulation in striated muscles, which are common characteristics of myofibrillar myopathy. We also found nuclear inclusions containing p62, ubiquitin, and SUMO proteins with nuclear envelope invaginations as a unique pathological hallmark in Dst-b mutation-induced cardiomyopathy. RNA-sequencing analysis revealed changes in expression of genes responsible for cardiovascular functions. In silico analysis identified DST-b alleles with nonsense mutations in populations worldwide, suggesting that some unidentified hereditary myopathy and cardiomyopathy are caused by DST-b mutations. Here, we demonstrate that the Dst-b isoform is essential for long-term maintenance of striated muscles.

    DOI: 10.7554/elife.78419

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    その他リンク: https://cdn.elifesciences.org/articles/78419/elife-78419-v1.xml

  • Perturbation of monoamine metabolism and enhanced fear responses in mice defective in the regeneration of tetrahydrobiopterin. 国際誌

    Katsuya Miyajima, Yusuke Sudo, Sho Sanechika, Yoshitaka Hara, Mieko Horiguchi, Feng Xu, Minori Suzuki, Satoshi Hara, Koichi Tanda, Ken-Ichi Inoue, Masahiko Takada, Nozomu Yoshioka, Hirohide Takebayashi, Masayo Mori-Kojima, Masahiro Sugimoto, Chiho Sumi-Ichinose, Kazunao Kondo, Keizo Takao, Tsuyoshi Miyakawa, Hiroshi Ichinose

    Journal of neurochemistry   161 ( 2 )   129 - 145   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Increasing evidence suggests the involvement of peripheral amino acid metabolism in the pathophysiology of neuropsychiatric disorders, whereas the molecular mechanisms are largely unknown. Tetrahydrobiopterin (BH4) is a cofactor for enzymes that catalyze phenylalanine metabolism, monoamine synthesis, nitric oxide production, and lipid metabolism. BH4 is synthesized from guanosine triphosphate and regenerated by quinonoid dihydropteridine reductase (QDPR), which catalyzes the reduction of quinonoid dihydrobiopterin. We analyzed Qdpr-/- mice to elucidate the physiological significance of the regeneration of BH4. We found that the Qdpr-/- mice exhibited mild hyperphenylalaninemia and monoamine deficiency in the brain, despite the presence of substantial amounts of BH4 in the liver and brain. Hyperphenylalaninemia was ameliorated by exogenously administered BH4, and dietary phenylalanine restriction was effective for restoring the decreased monoamine contents in the brain of the Qdpr-/- mice, suggesting that monoamine deficiency was caused by the secondary effect of hyperphenylalaninemia. Immunohistochemical analysis showed that QDPR was primarily distributed in oligodendrocytes but hardly detectable in monoaminergic neurons in the brain. Finally, we performed a behavioral assessment using a test battery. The Qdpr-/- mice exhibited enhanced fear responses after electrical foot shock. Taken together, our data suggest that the perturbation of BH4 metabolism should affect brain monoamine levels through alterations in peripheral amino acid metabolism, and might contribute to the development of anxiety-related psychiatric disorders. Cover Image for this issue: https://doi.org/10.1111/jnc.15398.

    DOI: 10.1111/jnc.15600

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  • Retrograde gene transfer into neural pathways mediated by adeno-associated virus (AAV)-AAV receptor interaction. 査読 国際誌

    Hiromi Sano, Kenta Kobayashi, Nozomu Yoshioka, Hirohide Takebayashi, Atsushi Nambu

    Journal of neuroscience methods   345   108887 - 108887   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Viral vector systems delivering transgenes in the retrograde direction through axons to neural cell bodies are powerful experimental tools for the functional analysis of specific neural pathways. Generally, the efficiency of viral vector-mediated retrograde gene transfer depends on the expression of requisite viral receptors in neural pathways projecting to the viral vector-injected regions. This is known as viral tropism and can limit the utility of retrograde viral vectors. The adeno-associated virus (AAV) vector has become an increasingly popular platform for gene delivery to neural cells in vivo, and it is therefore meaningful to develop a new type of retrograde gene transfer approach based on a tropism-free AAV vector system. NEW METHOD: The wild-type or mutant receptor gene of AAV was expressed to mitigate AAV tropism. RESULTS: Efficient AAV vector-mediated retrograde gene transfer was observed in diverse neural pathways by expression of the AAV receptor (AAVR) gene. Moreover, the expression of a minimal mutant of AAVR (miniAAVR), which maintains binding potential to AAV, demonstrated efficient retrograde gene expression comparable to that of AAVR. COMPARISON WITH EXISTING METHODS: The utility of existing AAV vector-mediated retrograde gene delivery methods is sometimes limited by tropism. Our newly developed AAV-AAVR and AAV-miniAAVR interaction approaches enabled efficient retrograde gene transfer into various neural pathways by mitigating tropism. CONCLUSIONS: AAV-AAVR and AAV-miniAAVR interaction approaches enabled us to induce efficient retrograde gene expression in targeted neural pathways and provide a powerful tool for analyzing specific neural pathways.

    DOI: 10.1016/j.jneumeth.2020.108887

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  • Disruption of dystonin in Schwann cells results in late-onset neuropathy and sensory ataxia. 査読 国際誌

    Masao Horie, Nozomu Yoshioka, Satoshi Kusumi, Hiromi Sano, Masayuki Kurose, Izumi Watanabe-Iida, Ibrahim Hossain, Satomi Chiken, Manabu Abe, Kensuke Yamamura, Kenji Sakimura, Atsushi Nambu, Masahiro Shibata, Hirohide Takebayashi

    Glia   68 ( 11 )   2330 - 2344   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dystonin (Dst) is a causative gene for Dystonia musculorum (dt) mice, which is an inherited disorder exhibiting dystonia-like movement and ataxia with sensory degeneration. Dst is expressed in a variety of tissues, including the central nervous system and the peripheral nervous system (PNS), muscles, and skin. However, the Dst-expressing cell type(s) for dt phenotypes have not been well characterized. To address the questions whether the disruption of Dst in Schwann cells induces movement disorders and how much impact does it have on dt phenotypes, we generated Dst conditional knockout (cKO) mice using P0-Cre transgenic mice and Dst gene trap mice. First, we assessed the P0-Cre transgene-dependent Cre recombination using tdTomato reporter mice and then confirmed the preferential tdTomato expression in Schwann cells. In the Dst cKO mice, Dst mRNA expression was significantly decreased in Schwann cells, but it was intact in most of the sensory neurons in the dorsal root ganglion. Next, we analyzed the phenotype of Dst cKO mice. They exhibited a normal motor phenotype during juvenile periods, and thereafter, started exhibiting an ataxia. Behavioral tests and electrophysiological analyses demonstrated impaired motor abilities and slowed motor nerve conduction velocity in Dst cKO mice, but these mice did not manifest dystonic movements. Electron microscopic observation of the PNS of Dst cKO mice revealed significant numbers of hypomyelinated axons and numerous infiltrating macrophages engulfing myelin debris. These results indicate that Dst is important for normal PNS myelin organization and Dst disruption in Schwann cells induces late-onset neuropathy and sensory ataxia. MAIN POINTS: Dystonin (Dst) disruption in Schwann cells results in late-onset neuropathy and sensory ataxia. Dst in Schwann cells is important for normal myelin organization in the peripheral nervous system.

    DOI: 10.1002/glia.23843

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  • Diverse dystonin gene mutations cause distinct patterns of Dst isoform deficiency and phenotypic heterogeneity in Dystonia musculorum mice. 査読 国際誌

    Nozomu Yoshioka, Yudai Kabata, Momona Kuriyama, Norihisa Bizen, Li Zhou, Dang M Tran, Masato Yano, Atsushi Yoshiki, Tatsuo Ushiki, Thomas J Sproule, Riichiro Abe, Hirohide Takebayashi

    Disease models & mechanisms   13 ( 5 )   2020年5月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Loss-of-function mutations in dystonin (DST) can cause hereditary sensory and autonomic neuropathy type 6 (HSAN-VI) or epidermolysis bullosa simplex (EBS). Recently, DST-related diseases were recognized to be more complex than previously thought because a patient exhibited both neurological and skin manifestations, whereas others display only one or the other. A single DST locus produces at least three major DST isoforms: DST-a (neuronal isoform), DST-b (muscular isoform) and DST-e (epithelial isoform). Dystonia musculorum (dt) mice, which have mutations in Dst, were originally identified as spontaneous mutants displaying neurological phenotypes. To reveal the mechanisms underlying the phenotypic heterogeneity of DST-related diseases, we investigated two mutant strains with different mutations: a spontaneous Dst mutant (Dstdt-23Rbrc mice) and a gene-trap mutant (DstGt mice). The Dstdt-23Rbrc allele possesses a nonsense mutation in an exon shared by all Dst isoforms. The DstGt allele is predicted to inactivate Dst-a and Dst-b isoforms but not Dst-e There was a decrease in the levels of Dst-a mRNA in the neural tissue of both Dstdt-23Rbrc and DstGt homozygotes. Loss of sensory and autonomic nerve ends in the skin was observed in both Dstdt-23Rbrc and DstGt mice at postnatal stages. In contrast, Dst-e mRNA expression was reduced in the skin of Dstdt-23Rbrc mice but not in DstGt mice. Expression levels of Dst proteins in neural and cutaneous tissues correlated with Dst mRNAs. Because Dst-e encodes a structural protein in hemidesmosomes (HDs), we performed transmission electron microscopy. Lack of inner plaques and loss of keratin filament invasions underneath the HDs were observed in the basal keratinocytes of Dstdt-23Rbrc mice but not in those of DstGt mice; thus, the distinct phenotype of the skin of Dstdt-23Rbrc mice could be because of failure of Dst-e expression. These results indicate that distinct mutations within the Dst locus can cause different loss-of-function patterns among Dst isoforms, which accounts for the heterogeneous neural and skin phenotypes in dt mice and DST-related diseases.

    DOI: 10.1242/dmm.041608

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  • Action Selection and Flexible Switching Controlled by the Intralaminar Thalamic Neurons. 査読 国際誌

    Shigeki Kato, Ryoji Fukabori, Kayo Nishizawa, Kana Okada, Nozomu Yoshioka, Masateru Sugawara, Yuko Maejima, Kenju Shimomura, Masahiro Okamoto, Satoshi Eifuku, Kazuto Kobayashi

    Cell reports   22 ( 9 )   2370 - 2382   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Learning processes contributing to appropriate selection and flexible switching of behaviors are mediated through the dorsal striatum, a key structure of the basal ganglia circuit. The major inputs to striatal subdivisions are provided from the intralaminar thalamic nuclei, including the central lateral nucleus (CL) and parafascicular nucleus (PF). Thalamostriatal neurons in the PF modulate the acquisition and performance of stimulus-response learning. Here, we address the roles of the CL thalamostriatal neurons in learning processes by using a selective neural pathway targeting technique. We show that the CL neurons are essential for the performance of stimulus-response learning and for behavioral flexibility, including reversal and attentional set-shifting of learned responses. In addition, chemogenetic suppression of neural activity supports the requirements of these neurons for behavioral flexibility. Our results suggest that the main contribution of the CL thalamostriatal neurons is functional control of the basal ganglia circuit linked to the prefrontal cortex.

    DOI: 10.1016/j.celrep.2018.02.016

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  • Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex 査読

    Xubin Hou, Nozomu Yoshioka, Hiroaki Tsukano, Akiko Sakai, Shinji Miyata, Yumi Watanabe, Yuchio Yanagawa, Kenji Sakimura, Kosei Takeuchi, Hiroshi Kitagawa, Takao K. Hensch, Katsuei Shibuki, Michihiro Igarashi, Sayaka Sugiyama

    SCIENTIFIC REPORTS   7 ( 1 )   12646   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.

    DOI: 10.1038/s41598-017-04007-x

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  • Motoneuron degeneration in the trigeminal motor nucleus innervating the masseter muscle in Dystonia musculorum mice. 査読

    Hossain MI, Horie M, Yoshioka N, Kurose M, Yamamura K, Takebayashi H

    Neurochemistry international   2017年10月

  • Abnormalities in perineuronal nets and behavior in mice lacking CSGalNAcT1, a key enzyme in chondroitin sulfate synthesis 査読

    Nozomu Yoshioka, Shinji Miyata, Atsushi Tamada, Yumi Watanabe, Asami Kawasaki, Hiroshi Kitagawa, Keizo Takao, Tsuyoshi Miyakawa, Kosei Takeuchi, Michihiro Igarashi

    MOLECULAR BRAIN   10 ( 1 )   47   2017年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC  

    Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans. In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions. To investigate the importance of CS, we produced and precisely examined mice that were deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO). Biochemical analysis of T1KO revealed that loss of this enzyme reduced the amount of CS by approximately 50% in various brain regions. The amount of CS in PNNs was also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, was not changed. In T1KO, we observed abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference. These results suggest that T1 is important for plasticity, probably due to regulation of CS-dependent PNNs, and that T1KO is a good model for investigation of PNNs.

    DOI: 10.1186/s13041-017-0328-5

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  • BPAG1 in muscles: Structure and function in skeletal, cardiac and smooth muscle 査読

    Masao Horie, Nozomu Yoshioka, Hirohide Takebayashi

    SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY   69   26 - 33   2017年9月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    BPAG1, also known as Dystonin or BP230, belongs to the plakin family of proteins, which has multiple cytoskeleton-binding domains. Several BPAG1 isoforms are produced by a single BPAG1 genomic locus using different promoters and exons. For example, BPAG1 a, BPAG1b, and BPAG1 e are predominantly expressed in the nervous system, muscle, and skin, respectively. Among BPAG1 isoforms, BPAG1 e is well studied because it was first identified as an autoantigen in patients with bullous pemphigoid, an autoimmune skin disease. BPAG1 e is a component of hemidesmosomes, the adhesion complexes that promote dermal-epidermal cohesion. In the nervous system, the role of BPAG1 a is also well studied because disruption of BPAG I a results in a phenotype identical to that of Dystonia musculorum (dt) mutants, which show progressive motor disorder. However, the expression and function of BPAG1 in muscles is not well studied. The aim of this review is to provide an overview of and highlight some recent findings on the expression and function of BPAG1 in muscles, which can assist future studies designed to delineate the role and regulation of BPAG1 in the dt mouse phenotype and in human hereditary sensory and autonomic neuropathy type 6 (HSAN6). (C) 2017 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.semcdb.2017.07.016

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  • An Extract of Chinpi, the Dried Peel of the Citrus Fruit Unshiu, Enhances Axonal Remyelination via Promoting the Proliferation of Oligodendrocyte Progenitor Cells 査読

    Hideaki Tokunaga, Chika Seiwa, Nozomu Yoshioka, Kazushige Mizoguchi, Masahiro Yamamoto, Hiroaki Asou, Sadakazu Aiso

    EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE   2016   8692698   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HINDAWI PUBLISHING CORP  

    The aging-induced decrease in axonal myelination/remyelination is due to impaired recruitment and differentiation of oligodendrocyte progenitor cells (OPCs). Our previous studies have shown that a monoclonal antibody to DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 (Ddx54), a member of the DEAD box family of RNA helicases, (1) specifically labels oligodendrocyte lineages, (2) binds to mRNA and protein isoforms of myelin basic proteins (MBP), and (3) regulates migration of OPCs from ventricular zone to corpus callosum in mice. It has also been demonstrated that specific loss of a 21.5 kDa MBP isoform (MBP21.5) reflects demyelination status, and oral administration of an extract of Chinpi, citrus unshiu peel, reversed the aging-induced demyelination. Here, we report that Chinpi treatment induced a specific increase in the MBP21.5, led to the reappearance of Ddx54-expressing cells in ventricular-subventricular zone and corpus callosum of aged mice, and promoted remyelination. Treatment of in vitro OPC cultures with Chinpi constituents, hesperidin plus narirutin, led to an increase in 5-bromo-2'-deoxyuridine incorporation in Ddx54-expressing OPCs, but not in NG2- or Olig2-expressing cell populations. The present study suggests that Ddx54 plays crucial role in remyelination. Furthermore, Chinpi and Chinpi-containing herbal medicines may be a therapeutic option for the aging-induced demyelination diseases.

    DOI: 10.1155/2016/8692698

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  • Expression of phosphorylated cyclic AMP response element-binding protein in melanin-concentrating hormone neurons and orexin neurons in male and female rats during ad-libitum feeding 査読

    Atsushi Fukushima, Hiroko Hagiwara, Nozomu Yoshioka, Fukuko Kimura, Tatsuo Akema, Toshiya Funabashi

    NEUROREPORT   25 ( 10 )   766 - 770   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Using phosphorylated cyclic AMP response element-binding protein (pCREB) as a marker of neural activity, we previously suggested that orexin neurons and melanin-concentrating hormone (MCH) neurons play distinct roles in feeding behavior. In the present study, we examined the expression of pCREB during ad-libitum feeding; previously, only fasted animals were examined. MCH neurons, but not orexin neurons, expressed pCREB during spontaneous food intake. The induction of pCREB expression did not differ by sex, but attenuation seemed to occur faster in females than in males. On the basis of the results of the present study, we speculate that MCH neurons respond to nutrition-related feeding, but the feeding-related activity of orexin was not evident unless hunger was accompanied by stress, such as the stress caused by the absence of food in the case of fasting. Therefore, the desire to eat under normal conditions does not drive orexin neurons, but it does drive MCH neurons. We tested this hypothesis by examining the effects of consuming glucose or saccharin, a nonmetabolized sweetener, in fasted male and female rats. Glucose and saccharin were equally effective in reducing pCREB expression in the orexin neurons of female rats. In MCH neurons, glucose attenuated the expression of pCREB, but saccharin had no effect, irrespective of sex. Taken together, the results indicate that MCH and orexin peptides play physiologically distinct roles in feeding behavior.

    DOI: 10.1097/WNR.0000000000000172

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  • LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes 査読

    Tetsuya Takano, Tomoki Urushibara, Nozomu Yoshioka, Taro Saito, Mitsunori Fukuda, Mineko Tomomura, Shin-ichi Hisanaga

    MOLECULAR BIOLOGY OF THE CELL   25 ( 11 )   1755 - 1768   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Neurons extend two types of neurites-axons and dendrites-that differ in structure and function. Although it is well understood that the cytoskeleton plays a pivotal role in neurite differentiation and extension, the mechanisms by which membrane components are supplied to growing axons or dendrites is largely unknown. We previously reported that the membrane supply to axons is regulated by lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the role of LMTK1 in dendrite formation. Downregulation of LMTK1 increases dendrite growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1 knockout significantly enhances the prevalence, velocity, and run length of anterograde movement of Rab11A-positive endosomes to levels similar to those expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics also increases in the cell body and growth cone of LMTK1-deficient neurons. Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth.

    DOI: 10.1091/mbc.E14-01-0675

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  • Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury 査読

    Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa Onaga, Yumi Watanabe, Shinji Miyata, Yoshino Wada, Chika Kudo, Masayasu Okada, Kentaro Ohko, Kanako Oda, Toshiya Sato, Minesuke Yokoyama, Natsuki Matsushita, Masaya Nakamura, Hideyuki Okano, Kenji Sakimura, Hitoshi Kawano, Hiroshi Kitagawa, Michihiro Igarashi

    NATURE COMMUNICATIONS   4   2740   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration-an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

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  • A DEAD-box RNA helicase Ddx54 protein in oligodendrocytes is indispensable for myelination in the central nervous system 査読

    Rui Zhan, Masahiro Yamamoto, Toshiyuki Ueki, Nozomu Yoshioka, Kayoko Tanaka, Hiromi Morisaki, Chika Seiwa, Yuta Yamamoto, Hitoshi Kawano, Yoshihiro Tsuruo, Kenji Watanabe, Hiroaki Asou, Sadakazu Aiso

    JOURNAL OF NEUROSCIENCE RESEARCH   91 ( 3 )   335 - 348   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    We recently reported that a new monoclonal antibody, 4F2, which labels oligodendroglial lineage cells, recognizes a DEAD-box RNA helicase Ddx54 and that Ddx54 binds to myelin basic protein (MBP) in brain and cultured oligodendrocytes. To elucidate the biological function of Ddx54, we generated a recombinant adenovirus, Ad-shRNA:Ddx54, expressing a short hairpin RNA to silence endogenous Ddx54 protein. The virus was intraventricularly injected into the brains of mice on postnatal day (PD) 2. The brains at PD 9 were then analyzed by immunohistochemistry. In untreated normal brain sections, as well as control brains that had been injected with Ad-beta-Gal, myelination of axons occurred in the corpus callosum with filamentous patterns of immunosignals of myelin-associated glycoprotein (MAG) and MBP. In Ad-shRNA:Ddx54-injected brain, substantial amounts of MAG and MBP immunosignals were present, but MBP immunosignals accumulated in the subplate layer and did not intrude into the emerging white matter. Immunoblot analysis revealed that Ddx54 knockdown caused a significant decrease in the level of 21.5 kDa MBP isoform and Ddx54, but the amount of Olig2; 2',3'-cyclic nucleotide 3' phosphodiesterase; MAG; three MBP isoforms (14, 17.5, and 18 kDa); and QKI-5, QKI-6, and QKI-7 proteins remained unchanged. Transfection of the Ddx54 expression vector into luciferase reporter-introduced neuroepithelial cells resulted in upregulated MBP promoter activity. Immunoprecipitation of Ddx54 protein in MBP-transfected HEK293 cells indicated that Ddx54 may directly interact with MBP mRNA. These results suggest that Ddx54 protein play an important role in central nervous system myelination, presumably in myelin sheath formation after the differentiation of oligodendrocytes. (c) 2012 Wiley Periodicals, Inc.

    DOI: 10.1002/jnr.23162

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  • Role of the lesion scar in the response to damage and repair of the central nervous system 査読

    Hitoshi Kawano, Junko Kimura-Kuroda, Yukari Komuta, Nozomu Yoshioka, Hong Peng Li, Koki Kawamura, Ying Li, Geoffrey Raisman

    CELL AND TISSUE RESEARCH   349 ( 1 )   169 - 180   2012年7月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.

    DOI: 10.1007/s00441-012-1336-5

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  • LMTK1/AATYK1 Is a Novel Regulator of Axonal Outgrowth That Acts via Rab11 in a Cdk5-Dependent Manner 査読

    Tetsuya Takano, Mineko Tomomura, Nozomu Yoshioka, Koji Tsutsumi, Yukichi Terasawa, Taro Saito, Hitoshi Kawano, Hiroyuki Kamiguchi, Mitsunori Fukuda, Shin-ichi Hisanaga

    JOURNAL OF NEUROSCIENCE   32 ( 19 )   6587 - 6599   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC NEUROSCIENCE  

    Axonal outgrowth is a coordinated process of cytoskeletal dynamics and membrane trafficking; however, little is known about proteins responsible for regulating the membrane supply. LMTK1 (lemur kinase 1)/AATYK1 (apoptosis-associated tyrosine kinase 1) is a serine/threonine kinase that is highly expressed in neurons. We recently reported that LMTK1 plays a role in recycling endosomal trafficking in CHO-K1 cells. Here we explore the role of LMTK1 in axonal outgrowth and its regulation by Cdk5 using mouse brain cortical neurons. LMTK1 was expressed and was phosphorylated at Ser34, the Cdk5 phosphorylation site, at the time of axonal outgrowth in culture and colocalized with Rab11A, the small GTPase that regulates recycling endosome traffic, at the perinuclear region and in the axon. Overexpression of the unphosphorylated mutant LMTK1-S34A dramatically promoted axonal outgrowth in cultured neurons. Enhanced axonal outgrowth was diminished by the inactivation of Rab11A, placing LMTK1 upstream of Rab11A. Unexpectedly, the downregulation of LMTK1 by knockdown or gene targeting also significantly enhanced axonal elongation. Rab11A-positive vesicles were transported anterogradely more quickly in the axons of LMTK1-deficient neurons than in those of wild-type neurons. The enhanced axonal outgrowth was reversed by LMTK1-WT or the LMTK1-S34D mutant, which mimics the phosphorylated state, but not by LMTK1-S34A. Thus, LMTK1 can negatively control axonal outgrowth by regulating Rab11A activity in a Cdk5-dependent manner, and Cdk5-LMTK1-Rab11 is a novel signaling pathway involved in axonal outgrowth.

    DOI: 10.1523/JNEUROSCI.5317-11.2012

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  • The astrocytic lineage marker calmodulin-regulated spectrin-associated protein 1 (Camsap1): Phenotypic heterogeneity of newly born Camsap1-expressing cells in injured mouse brain 査読

    Nozomu Yoshioka, Hiroaki Asou, Shin-Ichi Hisanaga, Hitoshi Kawano

    JOURNAL OF COMPARATIVE NEUROLOGY   520 ( 6 )   1301 - 1317   2012年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Calmodulin-regulated spectrin-associated protein 1 (Camsap1) has been recognized as a new marker for astrocytic lineage cells and is expressed on mature astrocytes in the adult brain (Yamamoto et al. [2009] J. Neurosci. Res. 87:503513). In the present study, we found that newly born Camsap1-expressing cells exhibited regional heterogeneity in an early phase after stab injury of the mouse brain. In the surrounding area of the lesion site, Camsap1 was expressed on quiescent astrocytes. At 3 days after injury, Camsap1 immunoreactivity was upregulated on glial fibrillary acidic protein-immunoreactive (GFAP-ir) astrocytes. Some of these astrocytes incorporated bromodeoxyuridine (BrdU) together with re-expression of the embryonic cytoskeleton protein nestin. In the neighboring region of the lesion cavity, Camsap1 was expressed on GFAP-negative cells. At 3 days after injury, GFAP-ir astrocytes were absent around the lesion cavity. At this stage, NG2-ir cells immunopositive for Camsap1 and immunonegative for GFAP were distributed in border of the lesion cavity. By 10 days, Camsap1 immunoreactivity was exclusively detected on GFAP-ir reactive astrocytes devoid of NG2 immunoreactivity. BrdU pulse-chase labeling assay suggested the differentiation of Camsap1+/NG2+ cells into Camsap1+/GFAP+ astrocytes. In the subependymal zone of the lateral ventricle, Camsap1-ir cells increased after injury. Camsap1 immunoreactivity was distributed on ependymal and subependymal cells bearing various astrocyte markers, and BrdU incorporation was enhanced on such Camsap1-ir cells after injury. These results suggest that newly born reactive astrocytes are derived from heterogeneous Camsap1-expressing cells in the injured brain. J. Comp. Neurol. 520:13011317, 2012. (C) 2011 Wiley Periodicals, Inc.

    DOI: 10.1002/cne.22788

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  • Small molecule inhibitor of type I transforming growth factor-β receptor kinase ameliorates the inhibitory milieu in injured brain and promotes regeneration of nigrostriatal dopaminergic axons. 査読

    Yoshioka N, Kimura-Kuroda J, Saito T, Kawamura K, Hisanaga S, Kawano H

    Journal of neuroscience research   89 ( 3 )   381 - 393   2011年3月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:3  

    DOI: 10.1002/jnr.22552

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  • Suppression of Fibrotic Scar Formation Promotes Axonal Regeneration Without Disturbing Blood-Brain Barrier Repair and Withdrawal of Leukocytes After Traumatic Brain Injury 査読

    Nozomu Yoshioka, Shin-Ichi Hisanaga, Hitoshi Kawano

    JOURNAL OF COMPARATIVE NEUROLOGY   518 ( 18 )   3867 - 3881   2010年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    The fibrotic scar containing type IV collagen (Col IV) formed in a lesion site is considered as an obstacle to axonal regeneration, because intracerebral injection of 2,2'-dipyridyl (DPY), an inhibitor of Col IV triple-helix formation, suppresses fibrotic scar formation in the lesion site and promotes axonal regeneration. To determine the role of the fibrotic scar on the healing process of injured central nervous system (CNS), the restoration of blood-brain barrier (BBB) and withdrawal of inflammatory leukocytes were examined in mice subjected to unilateral transection of the nigrostriatal dopaminergic pathway and intracerebral DPY injection. At 5 days after injury, destruction of BBB represented by leakage of Evans blue (EB) and widespread infiltration of CD45-immunoreactive leukocytes was observed around the lesion site, whereas reactive astrocytes increased surrounding the BBB-destroyed area. By 2 weeks after injury, the region of EB leakage and the diffusion of leukocytes were restricted to the inside of the fibrotic scar, and reactive astrocytes gathered around the fibrotic scar. In the DPY-treated lesion site, formation of the fibrotic scar was suppressed (84% decrease in Col IV-deposited area), reactive astrocytes occupied the lesion center, and areas of both EB leakage and leukocyte infiltration decreased by 86%. DPY treatment increased the number of regenerated dopaminergic axons by 2.53-fold. These results indicate that suppression of fibrotic scar formation does not disturb the healing process in damaged CNS, and suggest that this strategy is a reliable tool to promote axonal regeneration after traumatic injury in the CNS. J. Comp. Neurol. 518:3867-3881, 2010. (C) 2010 Wiley-Liss, Inc.

    DOI: 10.1002/cne.22431

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  • Transplantation of olfactory ensheathing cells promotes axonal regeneration in a rat model of spinal cord injury 査読

    Xichuan Teng, Nozomu Yoshioka, Junko Kimura-Kuroda, Koki Kawamura, Hitoshi Kawano, Hongpeng Li

    NEURAL REGENERATION RESEARCH   5 ( 9 )   651 - 656   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SHENYANG EDITORIAL DEPT NEURAL REGENERATION RES  

    BACKGROUND: Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery However, the mechanisms underlying the effects of OEC transplantation remain controversial
    OBJECTIVE: To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation, and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation
    DESIGN, TIME AND SETTING: A randomized, controlled animal expenment was performed at the Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan and at the Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, China between April 2007 and May 2009.
    MATERIALS: OECs were obtained from olfactory nerves and olfactory bulbs of male, 4-week-old, Sprague Dawley rats Rabbit anti-serotonin polyclonal antibody, rabbit anti-calcitonin gene-related peptide polyclonal antibody, rabbit anti-glial fibnllary acidic protein polyclonal antibody, rabbit anti-type IV collagen polyclonal antibody, and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used
    METHODS: Male, Sprague Dawley rats aged 8 weeks were randomly divided into three groups sham-surgery (n = 3), surgery (n = 9), and OEC transplantation (n = 11) Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-pL (1 x 105 cells) cell suspension.
    MAIN OUTCOME MEASURES: Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibnllary acidic protein and type IV collagen. Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry, respectively. Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels
    RESULTS: At 1 week after spinal cord injury, numerous glial cells were observed around the lesion site Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center, and descending serotonin- or ascending calcitonin gene-related peptidecontaining axons stopped at the fibrotic scar that was formed in the lesion site At 1 week after transplantation, the formation of fibrotic scar was significantly inhibited In addition, the fibrotic structure was partly formed and centralized in the blood vessel, and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site
    CONCLUSION: OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration

    DOI: 10.3969/j.issn.1673-5374.2010.09.002

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  • An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury 査読

    Junko Kimura-Kuroda, Xichuan Teng, Yukari Komuta, Nozomu Yoshioka, Kazunori Sango, Koki Kawamura, Geoffrey Raisman, Hitoshi Kawano

    MOLECULAR AND CELLULAR NEUROSCIENCE   43 ( 2 )   177 - 187   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    After central nervous system (CNS) injury, meningeal fibroblasts migrate in the lesion center to form a fibrotic scar which is surrounded by end feet of reactive astrocytes. The fibrotic scar expresses various axonal growth-inhibitory molecules and creates a major impediment for axonal regeneration. We developed an in vitro model of the scar using coculture of cerebral astrocytes and meningeal fibroblasts by adding transforming growth factor-beta 1 (TGF-beta 1), a potent fibrogenic factor. Addition of TGF-beta 1 to this coculture resulted in enhanced proliferation of fibroblasts and the formation of cell clusters which consisted of fibroblasts inside and surrounded by astrocytes. The cell cluster in culture densely accumulated the extracellular matrix molecules and axonal growth-inhibitory molecules similar to the fibrotic scar, and remarkably inhibited the neurite outgrowth of cerebellar neurons. Therefore, this culture system can be available to analyze the inhibitory property in the lesion site of CNS. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.mcn.2009.10.008

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  • dystonia musculorumマウスの運動失調に関わる神経回路異常の解析

    吉岡望, 黒瀬雅之, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   127th (CD-ROM)   2022年

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  • dystonia musculorumマウスの運動異常に関する神経回路基盤の解析

    吉岡望, 黒瀬雅之, 山村健介, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   125th   2020年

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  • 遺伝性感覚性自律神経性ニューロパチーVI型モデルマウスにおける末梢神経系選択的なdystonin発現回復の治療効果

    YOSHIOKA Nozomu, TAKEBAYASHI Hirohide

    日本神経化学会大会抄録集(Web)   62nd   2019年

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  • 末梢神経系におけるdystonin遺伝子トラップによる遺伝性感覚性自律神経性ニューロパチー6型の新規モデル動物の確立

    吉岡望, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   124th   194   2019年

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  • ミクログリアの先天性髄鞘形成不全に対する反応の組織化学的解析

    目黒玲子, 五十嵐恵介, 吉岡望, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   124th   192   2019年

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  • 単純性表皮水疱症モデルとしての新規Dystonin/Bpag1遺伝子変異マウスの解析

    栗山桃奈, 吉岡望, 加畑雄大, 加畑雄大, 牛木辰男, 吉木淳, SPROULE Thomas J, 阿部理一郎, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   123rd   110   2018年

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  • Dystonin遺伝子変異マウスにおける腎病変の組織学的解析

    降籏敏熙, 吉岡望, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   123rd   110   2018年

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  • 髄鞘形成不全マウスにおけるミクログリア分布及び形態の解析

    五十嵐恵介, 吉岡望, 竹林浩秀, 目黒玲子

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   123rd   140   2018年

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  • 末梢神経系特異的なDystonin KOマウスを用いた遺伝性ニューロパチーの病態解析

    吉岡望, 堀江正男, 竹林浩秀

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   123rd   142   2018年

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  • 皮質線条体路による意思決定の制御メカニズムの解析

    吉岡望, 加藤成樹, 小林和人

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   122nd   194   2017年

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  • ウイルスベクター二重感染法による皮質線条体ニューロンのサブタイプ選択的な遺伝子発現系の開発

    吉岡望, 加藤成樹, 菅原正晃, 加藤渚, 小林和人

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   121st   170   2016年

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  • 神経再生とGAP‐43分子のリン酸化制御の関係

    岡田正康, 岡田正康, 河嵜麻実, 吉岡望, 武内恒成, 武内恒成, 五十嵐道弘

    新潟医学会雑誌   129 ( 8 )   487‐488 - 488   2015年8月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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  • 脊髄損傷治療の現状とこれから 脊髄損傷後の軸索再生と組織修復—グリア瘢痕と線維性瘢痕の作用

    川野仁, 木村(黒田)純子, 小牟田縁, 吉岡望

    脳21   14 ( 2 )   114-118,96   2011年4月

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  • Importance of lesion scars in the tissue healing and inhibition of axonal regeneration after traumatic injury of the brain

    Nozomu Yoshioka, Hiroaki Asou, Junko Kimura-Kuroda, Shin-ichi Hisanaga, Hitoshi Kawano

    NEUROSCIENCE RESEARCH   71   E337 - E337   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2011.07.1479

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  • 中枢神経系の損傷部に形成される線維性瘢痕について III. 中枢神経系における創傷治癒と神経再生のメカニズム

    吉岡望, 久永眞市, 川野仁

    解剖学雑誌   85 ( Supplement )   194   2010年3月

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  • 中枢神経系の損傷部に形成される線維性瘢痕について I. 線維性瘢痕による神経再生の阻害

    川野仁, 小牟田縁, 吉岡望, 川村光毅

    解剖学雑誌   85 ( Supplement )   194   2010年3月

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  • 中枢神経系における組織修復と神経再生のメカニズムについて

    吉岡望, 阿相皓晃, 木村(黒田)純子, 久永眞市, 川野仁

    神経組織の成長・再生・移植研究会学術集会プログラム・予稿集   25th   58   2010年

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  • Fibrotic scar formed in the lesion site of the central nervous system. III. The mechanism underlying healing of neuronal tissue and axonal regeneration after brain trauma

    Nozomu Yoshioka, Hiroaki Asou, Junko Kimura-Kuroda, Shin-Ichi Hisanaga, Hitoshi Kawano

    NEUROSCIENCE RESEARCH   68   E255 - E255   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.1131

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  • Fibrotic scar formed in the lesion site of the central nervous system. I. Impediment for axonal regeneration

    Hitoshi Kawano, Junko Kimura-Kuroda, Nozomu Yoshioka, Yukari Komuta, Kazunori Sango, Koki Kawamura

    NEUROSCIENCE RESEARCH   68   E254 - E255   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.1129

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  • 培養系を用いた神経再生阻害モデルの確立

    木村(黒田)純子, 小牟田縁, 吉岡望, 川野仁

    神経組織の成長・再生・移植研究会学術集会プログラム・予稿集   25th   56   2010年

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  • 中枢神経系における神経再生阻害のメカニズム

    川野仁, 黒田(木村)純子, 小牟田縁, 吉岡望, 三五一憲

    神経組織の成長・再生・移植研究会学術集会プログラム・予稿集   25th   34   2010年

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    記述言語:日本語  

    J-GLOBAL

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  • 損傷後の中枢神経系における再生阻害のメカニズム

    川野仁, 滕錫川, 木村(黒田)純子, 小牟田縁, 吉岡望, 三五一憲, 川村光毅

    神経組織の成長・再生・移植研究会学術集会プログラム・予稿集   24th   74   2009年

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    記述言語:日本語  

    J-GLOBAL

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  • Involvement of glial and fibrotic scars in neural tissue repair after brain trauma

    Nozomu Yoshioka, Shin-Ichi Hisanaga, Hitoshi Kawano

    NEUROSCIENCE RESEARCH   65   S125 - S125   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.598

    Web of Science

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  • 脳外傷後の血液脳関門修復に果たす瘢痕組織の役割について

    吉岡望, 滕錫川, 小牟田縁, 久永眞市, 川野仁

    神経組織の成長・再生・移植研究会学術集会プログラム・予稿集   24th   76   2009年

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    記述言語:日本語  

    J-GLOBAL

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  • 48時間絶食雄性ラットのメラニン凝集ホルモン(MCH)ニューロンのリン酸化CREB(pCREB)発現に及ぼす甘味溶液飲水の影響

    吉岡望, 舩橋利也, 貴邑冨久子, 貴邑冨久子

    日本内分泌学会雑誌   82 ( 2 )   367   2006年9月

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    記述言語:日本語  

    J-GLOBAL

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講演・口頭発表等

  • dystonia musculorumマウスが示すジストニア様運動異常の神経基盤の解析

    吉岡 望

    第41回神経組織培養研究会  2019年11月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • dystonia musculorumマウスにおけるジストニア様運動異常の神経回路メカニズム 招待 国際会議

    吉岡 望

    Neuro2019 サテライトシンポジウム「大脳基底核の機能と疾患の新たな理解:基礎と臨床」  2019年7月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • 皮質線条体路による意思決定の制御機構-神経回路選択的な操作システムの開発から- 招待

    吉岡 望

    平成28年度 生理研研究会「行動を制御する神経ネットワーク機能の解明に向けて」  2016年12月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • 神経回路選択的な遺伝子操作による皮質線条体路の解析 招待

    吉岡 望

    平成28年度 第2回 大脳基底核機能研究会  2016年8月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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受賞

  • 解剖学会 奨励賞

    2022年12月   日本解剖学会   Dystonin遺伝子による神経・筋・皮膚の多臓器恒常性維持機構の解明

    吉岡 望

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  • 若手優秀発表賞

    2018年12月   次世代脳プロジェクト・冬のシンポジウム   運動異常を示すdystonia musculorumマウスの神経回路基盤の解析 -遺伝子トラップマウスを用いた選択的遺伝子改変法によるアプローチ-

    吉岡 望

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  • 若手優秀発表賞

    2012年7月   包括脳ネットワーク   損傷脳におけるコンドロイチン硫酸プロテオグリカンの産生メカニズム

    吉岡 望

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共同研究・競争的資金等の研究

  • 生命情報科学とマルチオミックス解析による新規筋疾患の包括的理解

    2022年9月 - 2023年3月

    新潟大学  令和4年度 U-goグラント 

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    担当区分:研究代表者 

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  • Dystonin-b遺伝子変異に起因する筋変性における分子病態機序の解明

    2022年6月 - 2023年3月

    公益財団法人 山口育英奨学会  令和4年度 学術研究助成金 

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    担当区分:研究代表者 

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  • 歩行障害のシステム理解に向けた下肢筋群の同時記録法と画像工学の融合研究

    2022年6月 - 2023年3月

    公益財団法人ユニオンツール育英奨学会  令和4年度 研究助成金 

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    担当区分:研究代表者 

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  • 生命情報科学と画像情報科学の融合研究による新規筋疾患の解明

    2021年9月 - 2022年3月

    新潟大学  令和3年度 U-goグラント 

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    担当区分:研究代表者 

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  • 画像工学と筋活動計測を用いた歩行運動の定量化と運動障害モデルへの応用

    2021年6月 - 2022年3月

    公益財団法人ユニオンツール育英奨学会  令和3年度 研究助成 

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    担当区分:研究代表者 

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  • 運動時の関連筋群からの活動計測法の確立と運動障害モデルへの応用

    2020年9月 - 2021年3月

    新潟大学  令和2年度 U-goグラント 

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    担当区分:研究代表者 

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  • ジストニアモデル動物を用いた不随意運動の神経回路基盤の解明と治療法の確立

    研究課題/領域番号:20K15912  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    吉岡 望

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 歩行障害と咀嚼障害の神経回路基盤の解明と治療的アプローチ

    2019年9月 - 2020年3月

    新潟大学  令和元年度 U-goグラント 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • 遺伝性ニューロパチーの病態解明ならび遺伝子治療法の応用-遺伝子トラップマウスを用いた選択的遺伝子改変法によるアプローチ-

    2019年4月 - 2021年10月

    一般財団法人 藤井節郎記念 大阪基礎医学研究奨励会  平成31年度 研究助成金 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • 神経回路選択的な細胞標識法による不随運動を司る神経基盤の解明

    2018年5月 - 2018年12月

    BioLegend  LEGEND Research Grant 2017年(後期) 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • ゲノム編集技術を活用した筋組織の生理機能と恒常性維持におけるDystoninの機能解明

    2018年3月 - 2019年3月

    中冨健康科学振興財団  中冨健康科学振興財団 研究助成金 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • 意思決定の習慣化を司る脳神経回路:皮質線条体路を起点とした脳内ネットワークの解明

    研究課題/領域番号:17K14951  2017年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    吉岡 望

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    動物は、学習を重ねることで結果を予測しながら臨機応変に行動する“目標指向型”の意思決定から、繰り返した行動を自動的に実行する“習慣型”の意思決定に切り替えて円滑な行動を可能にする。目標指向型の意思決定には、眼窩前頭皮質などの前頭前皮質から起こる皮質線条体路の関与が報告されているが、習慣型の意思決定における皮質線条体路の関与は殆ど分かっていない。本研究では、意思決定の習慣化を司る脳神経回路として、皮質線条体路に着目し、神経路選択的な遺伝子発現システムを応用した機能解析を実施した。

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  • 神経回路選択的な遺伝子操作技術による皮質線条体ニューロンの解析:行動選択の神経回路メカニズムとは?

    2015年12月 - 2016年11月

    公益財団法人カシオ科学振興財団  公益財団法人カシオ科学振興財団研究助成 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • 神経回路選択的な糖鎖改変技術の開発:学習・記憶における糖鎖多様性の意義とは?

    2015年4月 - 2016年11月

    日本科学協会  笹川科学研究助成 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • 神経可塑性における糖鎖の役割とは?:コンドロイチン硫酸合成酵素欠損マウスからのアプローチ

    2013年9月 - 2014年3月

    新潟大学  新潟大学プロジェクト推進経費(奨励研究) 

    吉岡 望

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    担当区分:研究代表者  資金種別:競争的資金

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  • TGF-β阻害剤と嗅球グリア細胞遅延移植による脊髄再生メカニズムの解明

    研究課題/領域番号:11J04608  2011年 - 2012年

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    吉岡 望

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    配分額:1300000円 ( 直接経費:1300000円 )

    昨年度は、損傷を受けた中枢神経系において軸索再生阻害因子であるコンドロイチン硫酸プロテオグリカン(CSPG)が損傷部に蓄積するメカニズムを解析した。本年度は、CSPGの再生阻害機構を解明するために、コンドロイチン硫酸合成酵素欠損マウスの形態学的解析を実施した。受入研究室では、コンドロイチン硫酸合成酵素を欠損した遺伝子改変マウスを作成しているが、このマウスではコンドロイチン硫酸産生量が約半分まで減少しており、脊髄損傷後の軸索再生が促進されることを確認していた。今回、この遺伝子改変マウスの脳・脊髄では、コンドロイチン硫酸の集積部位においてCS認識抗体による染色性が著明に低下することを見出した。一方で、コア蛋白質の発現変動はコンドロイチン硫酸ほど明瞭ではなく、多くの領域で正常であった。以上の結果、CSPGによる軸索再生阻害効果は、コア蛋白質でなくコンドロイチン硫酸によるものと示唆された。
    2年間の研究によって、当初の目的通り、TGF-β阻害剤と嗅球グリア細胞移植による軸索再生促進のメカニズムを解明できた(Yoshioka et al.,J Neurosci Res,2011)。つまり、損傷後に発現上昇するCSPGによって軸索再生が阻害されること、さらに、TGF-β阻害剤と細胞移植は両方ともCSPG発現を抑制することで軸索再生を促進することを見出した。次に、CSPGの発現制御機構を解析して、損傷部に集積するグリア前駆細胞においてCSPGの発現が特に高いことを見出した(Yoshioka et al.,J Comp Neurol,2012)。最終的には、CSPG合成に重要な遺伝子を欠損した遺伝子改変マウスの解析を通じて、CSPGがどの様に軸索再生を阻害するかについて分子レベルで明らかにした。

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担当経験のある授業科目(researchmap)

  • 医学研究実習

    機関名:新潟大学

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  • 基礎上級プログラム

    機関名:福島県立医科大学

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  • PBLチュートリアル

    機関名:福島県立医科大学

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  • 神経解剖学講義

    機関名:新潟大学

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  • 神経解剖実習

    機関名:新潟大学

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