Updated on 2025/07/12

写真a

 
UENO Masaki
 
Organization
Brain Research Institute Professor
Title
Professor
Homepage
http://www.bri.niigata-u.ac.jp/~system_neurodis/ueno/home-e.html
External link

Degree

  • Veterinary Medicine ( 2006.3   The University of Tokyo )

Research Interests

  • 神経発生

  • 神経再生

  • 神経可塑性

Research Areas

  • Life Science / Anatomy and histopathology of nervous system

Research History (researchmap)

  • Brain Research Institute, Niigata University   Professor

    2021.6

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  • Brain Research Institute, Niigata University   Professor (tenure track)

    2018.10 - 2021.5

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  • Brain Research Institute, Niigata University   Specially Appointed Professor

    2016.9 - 2018.9

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  • Japan Science and Technology Agency   PRESTO Researcher

    2013.9 - 2017.3

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  • JSPS   Postdoctral Fellowship for Research Abroad

    2012.8 - 2013.9

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  • Cincinnati Children's Hospital Medical Center   Division of Developmental Biology   Visiting Researcher

    2012.4 - 2017.1

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  • Osaka University   Graduate School of Medicine   Assistant Professor

    2008.4 - 2012.3

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  • Osaka University   Graduate School of Medicine   Postdoctoral fellow

    2007.12 - 2008.3

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  • Graduate School of Medicine, Chiba University   Postdoctoral fellow

    2007.8 - 2007.11

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  • RIKEN Brain Science Institute   Researcher

    2006.4 - 2007.7

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences

    2002.4 - 2006.3

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  • The University of Tokyo   Veterinary Medical Science

    2002.3

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Research History

  • Niigata University   Brain Research Institute Basic Neuroscience Branch   Professor

    2020.4

  • Niigata University   Brain Research Institute Center for Bioresources   Professor

    2018.10 - 2020.3

  • Niigata University   Brain Research Institute   Specially Appointed Professor

    2016.9 - 2018.9

Professional Memberships

Studying abroad experiences

  • Cincinnati Children's Hospital Medical Center   Visiting Researcher

    2012.4 - 2017.1

Qualification acquired

  • Veterinarian

 

Papers

  • TDP-43 mutants with different aggregation properties exhibit distinct toxicity, axonal transport, and secretion for disease progression in a mouse ALS/FTLD model Reviewed

    Hideki Mori, Tokiharu Sato, Shintaro Tsuboguchi, Masahiko Takahashi, Yuka Nakamura, Kana Hoshina, Taisuke Kato, Masahiro Fujii, Osamu Onodera, Masaki Ueno

    Neurobiology of Disease   212   106988 - 106988   2025.8

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    Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.nbd.2025.106988

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  • The diversity and plasticity of descending motor pathways rewired after stroke and trauma in rodents Reviewed

    Takahiro Inoue, Masaki Ueno

    Frontiers in Neural Circuits   19   2025.3

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    Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    Descending neural pathways to the spinal cord plays vital roles in motor control. They are often damaged by brain injuries such as stroke and trauma, which lead to severe motor impairments. Due to the limited capacity for regeneration of neural circuits in the adult central nervous system, currently no essential treatments are available for complete recovery. Notably, accumulating evidence shows that residual circuits of the descending pathways are dynamically reorganized after injury and contribute to motor recovery. Furthermore, recent technological advances in cell-type classification and manipulation have highlighted the structural and functional diversity of these pathways. Here, we focus on three major descending pathways, namely, the corticospinal tract from the cerebral cortex, the rubrospinal tract from the red nucleus, and the reticulospinal tract from the reticular formation, and summarize the current knowledge of their structures and functions, especially in rodent models (mice and rats). We then review and discuss the process and patterns of reorganization induced in these pathways following injury, which compensate for lost connections for recovery. Understanding the basic structural and functional properties of each descending pathway and the principles of the induction and outcome of the rewired circuits will provide therapeutic insights to enhance interactive rewiring of the multiple descending pathways for motor recovery.

    DOI： 10.3389/fncir.2025.1566562

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  • Scg2 drives reorganization of the corticospinal circuit with spinal premotor interneurons to recover motor function after stroke

    Tokiharu Sato, Yuka Nakamura, Kana Hoshina, Ken-ichi Inoue, Masahiko Takada, Masato Yano, Hitoshi Matsuzawa, Masaki Ueno

    bioRxiv   2025.1

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    Authorship：Corresponding author  

    DOI： 10.1101/2025.01.21.634186

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  • CRISPR/CasRx suppresses KRAS-induced brain arteriovenous malformation developed in postnatal brain endothelial cells in mice. Reviewed International journal

    Shoji Saito, Yuka Nakamura, Satoshi Miyashita, Tokiharu Sato, Kana Hoshina, Masayasu Okada, Hitoshi Hasegawa, Makoto Oishi, Yukihiko Fujii, Jakob Körbelin, Yoshiaki Kubota, Kazuki Tainaka, Manabu Natsumeda, Masaki Ueno

    JCI insight   9 ( 22 )   2024.11

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

    Brain arteriovenous malformations (bAVMs) are anomalies forming vascular tangles connecting the arteries and veins, which cause hemorrhagic stroke in young adults. Current surgical approaches are highly invasive, and alternative therapeutic methods are warranted. Recent genetic studies identified KRAS mutations in endothelial cells of bAVMs; however, the underlying process leading to malformation in the postnatal stage remains unknown. Here we established a mouse model of bAVM developing during the early postnatal stage. Among 4 methods tested, mutant KRAS specifically introduced in brain endothelial cells by brain endothelial cell-directed adeno-associated virus (AAV) and endothelial cell-specific Cdh5-CreERT2 mice successfully induced bAVMs in the postnatal period. Mutant KRAS led to the development of multiple vascular tangles and hemorrhage in the brain with increased MAPK/ERK signaling and growth in endothelial cells. Three-dimensional analyses in cleared tissue revealed dilated vascular networks connecting arteries and veins, similar to human bAVMs. Single-cell RNA-Seq revealed dysregulated gene expressions in endothelial cells and multiple cell types involved in the pathological process. Finally, we employed CRISPR/CasRx to knock down mutant KRAS expression, which efficiently suppressed bAVM development. The present model reveals pathological processes that lead to postnatal bAVMs and demonstrates the efficacy of therapeutic strategies with CRISPR/CasRx.

    DOI： 10.1172/jci.insight.179729

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  • TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models. Reviewed International journal

    Shintaro Tsuboguchi, Yuka Nakamura, Tomohiko Ishihara, Taisuke Kato, Tokiharu Sato, Akihide Koyama, Hideki Mori, Yuka Koike, Osamu Onodera, Masaki Ueno

    Acta neuropathologica   2023.8

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

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by TDP-43 inclusions in the cortical and spinal motor neurons. It remains unknown whether and how pathogenic TDP-43 spreads across neural connections to progress degenerative processes in the cortico-spinal motor circuitry. Here we established novel mouse ALS models that initially induced mutant TDP-43 inclusions in specific neuronal or cell types in the motor circuits, and investigated whether TDP-43 and relevant pathological processes spread across neuronal or cellular connections. We first developed ALS models that primarily induced TDP-43 inclusions in the corticospinal neurons, spinal motor neurons, or forelimb skeletal muscle, by using adeno-associated virus (AAV) expressing mutant TDP-43. We found that TDP-43 induced in the corticospinal neurons was transported along the axons anterogradely and transferred to the oligodendrocytes along the corticospinal tract (CST), coinciding with mild axon degeneration. In contrast, TDP-43 introduced in the spinal motor neurons did not spread retrogradely to the cortical or spinal neurons; however, it induced an extreme loss of spinal motor neurons and subsequent degeneration of neighboring spinal neurons, suggesting a degenerative propagation in a retrograde manner in the spinal cord. The intraspinal degeneration further led to severe muscle atrophy. Finally, TDP-43 induced in the skeletal muscle did not propagate pathological events to spinal neurons retrogradely. Our data revealed that mutant TDP-43 spread across neuro-glial connections anterogradely in the corticospinal pathway, whereas it exhibited different retrograde degenerative properties in the spinal circuits. This suggests that pathogenic TDP-43 may induce distinct antero- and retrograde mechanisms of degeneration in the motor system in ALS.

    DOI： 10.1007/s00401-023-02615-8

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  • Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord. Reviewed International journal

    Yuka Nakamura, Miyuki Kurabe, Mami Matsumoto, Tokiharu Sato, Satoshi Miytashita, Kana Hoshina, Yoshinori Kamiya, Kazuki Tainaka, Hitoshi Matsuzawa, Nobuhiko Ohno, Masaki Ueno

    eLife   12   2023.2

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

    Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 μm in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons around the central canal and within the axon bundles. Chemogenetic CSF-cNs inactivation reduced speed and step frequency during treadmill locomotion. Our data revealed the basic structures and connections of mouse CSF-cNs to control spinal motor circuits for proper locomotion. The versatile methods developed in this study will contribute to further understanding of CSF-cN functions in mammals.

    DOI： 10.7554/eLife.83108

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  • Modulation of Both Intrinsic and Extrinsic Factors Additively Promotes Rewiring of Corticospinal Circuits after Spinal Cord Injury. Reviewed International journal

    Yuka Nakamura, Masaki Ueno, Jesse K Niehaus, Richard A Lang, Yi Zheng, Yutaka Yoshida

    The Journal of neuroscience : the official journal of the Society for Neuroscience   41 ( 50 )   10247 - 10260   2021.12

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

    Axon regeneration after spinal cord injury (SCI) is limited by both a decreased intrinsic ability of neurons to grow axons and the growth-hindering effects of extrinsic inhibitory molecules expressed around the lesion. Deletion of phosphatase and tensin homolog (Pten) augments mechanistic target of rapamycin (mTOR) signaling and enhances the intrinsic regenerative response of injured corticospinal neurons after SCI. Because of the variety of growth-restrictive extrinsic molecules, it remains unclear how inhibition of conserved inhibitory signaling elements would affect axon regeneration and rewiring after SCI. Moreover, it remains unknown how a combinatorial approach to modulate both extrinsic and intrinsic mechanisms can enhance regeneration and rewiring after SCI. In the present study, we deleted RhoA and RhoC, which encode small GTPases that mediate growth inhibition signals of a variety of extrinsic molecules, to remove global extrinsic pathways. RhoA/RhoC double deletion in mice suppressed retraction or dieback of corticospinal axons after SCI. In contrast, Pten deletion increased regrowth of corticospinal axons into the lesion core. Although deletion of both RhoA and Pten did not promote axon regrowth across the lesion or motor recovery, it additively promoted rewiring of corticospinal circuits connecting the cerebral cortex, spinal cord, and hindlimb muscles. Our genetic findings, therefore, reveal that a combinatorial approach to modulate both intrinsic and extrinsic factors can additively promote neural circuit rewiring after SCI.SIGNIFICANCE STATEMENT SCI often causes severe motor deficits because of damage to the corticospinal tract (CST), the major neural pathway for voluntary movements. Regeneration of CST axons is required to reconstruct motor circuits and restore functions; however, a lower intrinsic ability to grow axons and extrinsic inhibitory molecules severely limit axon regeneration in the CNS. Here, we investigated whether suppression of extrinsic inhibitory cues by genetic deletion of Rho as well as enhancement of the intrinsic pathway by deletion of Pten could enable axon regrowth and rewiring of the CST after SCI. We show that simultaneous elimination of extrinsic and intrinsic signaling pathways can additively promote axon sprouting and rewiring of the corticospinal circuits. Our data demonstrate a potential molecular approach to reconstruct motor pathways after SCI.

    DOI： 10.1523/JNEUROSCI.2649-20.2021

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  • Restoring neuro-immune circuitry after brain and spinal cord injuries. Reviewed International journal

    Masaki Ueno

    International immunology   33 ( 6 )   311 - 325   2021.6

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

    Neuro-immune interactions are essential for our body's defense and homeostasis. Anatomical and physiological analyses have shown that the nervous system comprises multiple pathways that regulate the dynamics and functions of immune cells, which are mainly mediated by the autonomic nervous system and adrenal signals. These are disturbed when the neurons and circuits are damaged by diseases of the central nervous system (CNS). Injuries caused by stroke or trauma often cause immune dysfunction by abrogation of the immune-regulating neural pathways, which leads to an increased risk of infections. Here, I review the structures and functions of the neural pathways connecting the brain and the immune system, and the neurogenic mechanisms of immune dysfunction that emerge after CNS injuries. Recent technological advances in manipulating specific neural circuits have added mechanistic aspects of neuro-immune interactions and their dysfunctions. Understanding the neural bases of immune control and their pathological processes will deepen our knowledge of homeostasis and lead to the development of strategies to cure immune deficiencies observed in various CNS disorders.

    DOI： 10.1093/intimm/dxab017

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  • Lesion Area in the Cerebral Cortex Determines the Patterns of Axon Rewiring of Motor and Sensory Corticospinal Tracts After Stroke. Reviewed International journal

    Tokiharu Sato, Yuka Nakamura, Akinori Takeda, Masaki Ueno

    Frontiers in neuroscience   15   737034 - 737034   2021

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

    The corticospinal tract (CST) is an essential neural pathway for reorganization that recovers motor functions after brain injuries such as stroke. CST comprises multiple pathways derived from different sensorimotor areas of the cerebral cortex; however, the patterns of reorganization in such complex pathways postinjury are largely unknown. Here we comprehensively examined the rewiring patterns of the CST pathways of multiple cerebral origins in a mouse stroke model that varied in size and location in the sensorimotor cortex. We found that spared contralesional motor and sensory CST axons crossed the midline and sprouted into the denervated side of the cervical spinal cord after stroke in a large cortical area. In contrast, the contralesional CST fibers did not sprout in a small stroke, whereas the ipsilesional axons from the spared motor area grew on the denervated side. We further showed that motor and sensory CST axons did not innervate the projecting areas mutually when either one was injured. The present results reveal the basic principles that generate the patterns of CST rewiring, which depend on stroke location and CST subtype. Our data indicate the importance of targeting different neural substrates to restore function among the types of injury.

    DOI： 10.3389/fnins.2021.737034

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  • Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury. Reviewed International journal

    Naoki Sada, Yuki Fujita, Nanano Mizuta, Masaki Ueno, Takahisa Furukawa, Toshihide Yamashita

    Cell death & disease   11 ( 8 )   655 - 655   2020.8

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    Brain injury causes serious motor, sensory, and cognitive disabilities. Accumulating evidence has demonstrated that histone deacetylase (HDAC) inhibitors exert neuroprotective effects against various insults to the central nervous system (CNS). In this study, we investigated the effects of the HDAC inhibition on the expression of brain-derived neurotrophic factor (BDNF) and functional recovery after traumatic brain injury (TBI) in mice. Administration of class I HDAC inhibitor increased the number of synaptic boutons in rewiring corticospinal fibers and improved the recovery of motor functions after TBI. Immunohistochemistry results showed that HDAC2 is mainly expressed in the neurons of the mouse spinal cord under normal conditions. After TBI, HDAC2 expression was increased in the spinal cord after 35 days, whereas BDNF expression was decreased after 42 days. Administration of CI-994 increased BDNF expression after TBI. Knockdown of HDAC2 elevated H4K5ac enrichment at the BDNF promoter, which was decreased following TBI. Together, our findings suggest that HDAC inhibition increases expression of neurotrophic factors, and promote neuronal rewiring and functional recovery following TBI.

    DOI： 10.1038/s41419-020-02897-w

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  • Olig2-Induced Semaphorin Expression Drives Corticospinal Axon Retraction After Spinal Cord Injury. Reviewed International journal

    Masaki Ueno, Yuka Nakamura, Hiroshi Nakagawa, Jesse K Niehaus, Mari Maezawa, Zirong Gu, Atsushi Kumanogoh, Hirohide Takebayashi, Qing Richard Lu, Masahiko Takada, Yutaka Yoshida

    Cerebral cortex (New York, N.Y. : 1991)   30 ( 11 )   5702 - 5716   2020.6

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

    Axon regeneration is limited in the central nervous system, which hinders the reconstruction of functional circuits following spinal cord injury (SCI). Although various extrinsic molecules to repel axons following SCI have been identified, the role of semaphorins, a major class of axon guidance molecules, has not been thoroughly explored. Here we show that expression of semaphorins, including Sema5a and Sema6d, is elevated after SCI, and genetic deletion of either molecule or their receptors (neuropilin1 and plexinA1, respectively) suppresses axon retraction or dieback in injured corticospinal neurons. We further show that Olig2+ cells are essential for SCI-induced semaphorin expression, and that Olig2 binds to putative enhancer regions of the semaphorin genes. Finally, conditional deletion of Olig2 in the spinal cord reduces the expression of semaphorins, alleviating the axon retraction. These results demonstrate that semaphorins function as axon repellents following SCI, and reveal a novel transcriptional mechanism for controlling semaphorin levels around injured neurons to create zones hostile to axon regrowth.

    DOI： 10.1093/cercor/bhaa142

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  • Combinational Approach of Genetic SHP-1 Suppression and Voluntary Exercise Promotes Corticospinal Tract Sprouting and Motor Recovery Following Brain Injury. Reviewed International journal

    Takashi Tanaka, Tetsufumi Ito, Megumi Sumizono, Munenori Ono, Nobuo Kato, Satoru Honma, Masaki Ueno

    Neurorehabilitation and neural repair   34 ( 6 )   558 - 570   2020.6

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

    Background. Brain injury often causes severe motor dysfunction, leading to difficulties with living a self-reliant social life. Injured neural circuits must be reconstructed to restore functions, but the adult brain is limited in its ability to restore neuronal connections. The combination of molecular targeting, which enhances neural plasticity, and rehabilitative motor exercise is an important therapeutic approach to promote neuronal rewiring in the spared circuits and motor recovery. Objective. We tested whether genetic reduction of Src homology 2-containing phosphatase-1 (SHP-1), an inhibitor of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, has synergistic effects with rehabilitative training to promote reorganization of motor circuits and functional recovery in a mouse model of brain injury. Methods. Rewiring of the corticospinal circuit was examined using neuronal tracers following unilateral cortical injury in control mice and in Shp-1 mutant mice subjected to voluntary exercise. Recovery of motor functions was assessed using motor behavior tests. Results. We found that rehabilitative exercise decreased SHP-1 and increased BDNF and TrkB expression in the contralesional motor cortex after the injury. Genetic reduction of SHP-1 and voluntary exercise significantly increased sprouting of corticospinal tract axons and enhanced motor recovery in the impaired forelimb. Conclusions. Our data demonstrate that combining voluntary exercise and SHP-1 suppression promotes motor recovery and neural circuit reorganization after brain injury.

    DOI： 10.1177/1545968320921827

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  • Ghrelin-insulin-like growth factor-1 axis is activated via autonomic neural circuits in the non-alcoholic fatty liver disease. Reviewed International journal

    Takuro Nagoya, Kenya Kamimura, Ryosuke Inoue, Masayoshi Ko, Takashi Owaki, Yusuke Niwa, Norihiro Sakai, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Yuka Nakamura, Masaki Ueno, Shuji Terai

    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society   32 ( 5 )   e13799   2020.5

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

    BACKGROUND: The correlation of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) with non-alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter-organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH-releasing hormone and IGF-1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD. METHODS: The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF-1 were examined in NAFLD models of choline-deficient defined l-amino-acid diet-fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach. KEY RESULTS: The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF-1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits. CONCLUSIONS: Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF-1 from the liver.

    DOI： 10.1111/nmo.13799

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  • Netrin-G1 Regulates Microglial Accumulation along Axons and Supports the Survival of Layer V Neurons in the Postnatal Mouse Brain. Reviewed International journal

    Yuki Fujita, Toru Nakanishi, Masaki Ueno, Shigeyoshi Itohara, Toshihide Yamashita

    Cell reports   31 ( 4 )   107580 - 107580   2020.4

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    Microglia, the resident immune cells of the central nervous system, accumulate along subcerebral projection axons and support neuronal survival during the early postnatal period. It remains unknown how microglia follow an axon-specific distribution pattern to maintain neural circuits. Here, we investigated the mechanisms of microglial accumulation along subcerebral projection axons that were necessary for microglial accumulation in the internal capsule. Screening of molecules involved in this accumulation of microglia to axons of layer V cortical neurons identified netrin-G1, a member of the netrin family of axon guidance molecules with a glycosyl-phosphatidylinositol anchor. Deletion or knockdown of the netrin-G1 gene Ntng1 reduced microglial accumulation and caused loss of cortical neurons. Netrin-G1 ligand-Ngl1 knockout-mice-derived microglia showed reduced accumulation along the axons compared with wild-type microglia. Thus, microglia accumulate around the subcerebral projection axons via NGL1-netrin-G1 signaling and support neuronal survival. Our observations unveil bidirectional neurotrophic interactions between neurons and microglia.

    DOI： 10.1016/j.celrep.2020.107580

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  • Dual functions of microglia in the formation and refinement of neural circuits during development. Reviewed International journal

    Konishi H, Kiyama H, Ueno M

    International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience   77   18 - 25   2019.10

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

    Microglia colonize the central nervous system (CNS) parenchyma during embryogenesis and contribute to various developmental processes leading to the formation of refined neural circuits. In this review, we focus on the bidirectional function of microglia during normal CNS development and discuss recent perspectives on the functions of microglia in neural circuit formation. Microglia participate in neurogenesis, migration, axonal growth, and synapse formation and remodeling, all of which are fundamental for the establishment of neural networks, by secreting a variety of molecules toward neurons and phagocytosing both live and dying neurons or their debris. Intriguingly, microglia play dual roles in each of the neurodevelopmental processes that they affect. For instance, microglia modulate synapse numbers by both promoting the formation of new synapses and eliminating unnecessary synapses. The study of the developmental roles of microglia is essential not only for understanding normal CNS development but also for preventing developmental brain disorders caused by microglial dysfunction.

    DOI： 10.1016/j.ijdevneu.2018.09.009

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  • Skilled Movements in Mice Require Inhibition of Corticospinal Axon Collateral Formation in the Spinal Cord by Semaphorin Signaling. Reviewed

    Zirong Gu, Masaki Ueno, Kelsey Klinefelter, Madhulika Mamidi, Takeshi Yagi, Yutaka Yoshida

    The Journal of neuroscience : the official journal of the Society for Neuroscience   39 ( 45 )   8885 - 8899   2019.9

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    DOI： 10.1523/jneurosci.2832-18.2019

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  • Corticospinal Circuits from the Sensory and Motor Cortices Differentially Regulate Skilled Movements through Distinct Spinal Interneurons Reviewed

    Masaki Ueno, Yuka Nakamura, Jie Li, Zirong Gu, Jesse Niehaus, Mari Maezawa, Steven A. Crone, Martyn Goulding, Mark L. Baccei, Yutaka Yoshida

    Cell Reports   23 ( 5 )   1286 - 1300.e7   2018.5

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

    DOI： 10.1016/j.celrep.2018.03.137

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  • MARCKSL1 Regulates Spine Formation in the Amygdala and Controls the Hypothalamic-Pituitary-Adrenal Axis and Anxiety-Like Behaviors Reviewed

    Takashi Tanaka, Shoko Shimizu, Masaki Ueno, Yoshitaka Fujihara, Masahito Ikawa, Shingo Miyata

    EBioMedicine   30   62 - 73   2018.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

    DOI： 10.1016/j.ebiom.2018.03.018

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  • Control of species-dependent cortico-motoneuronal connections underlying manual dexterity Reviewed

    Zirong Gu, John Kalamboglas, Shin Yoshioka, Wenqi Han, Zhuo Li, Yuka Imamura Kawasawa, Sirisha Pochareddy, Zhen Li, Fuchen Liu, Xuming Xu, Sagara Wijeratne, Masaki Ueno, Emily Blatz, Joseph Salomone, Atsushi Kumanogoh, Mladen-Roko Rasin, Brian Gebelein, Matthew T. Weirauch, Nenad Sestan, John H. Martin, Yutaka Yoshida

    SCIENCE   357 ( 6349 )   400 - 404   2017.7

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

    DOI： 10.1126/science.aan3721

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  • Skilled Movements Require Non-apoptotic Bax/Bak Pathway-Mediated Corticospinal Circuit Reorganization Reviewed

    Zirong Gu, Najet Serradj, Masaki Ueno, Mishi Liang, Jie Li, Mark L. Baccei, John H. Martin, Yutaka Yoshida

    NEURON   94 ( 3 )   626 - +   2017.5

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

    DOI： 10.1016/j.neuron.2017.04.019

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  • Silencing spinal interneurons inhibits immune suppressive autonomic reflexes caused by spinal cord injury Reviewed

    Masaki Ueno, Yuka Ueno-Nakamura, Jesse Niehaus, Phillip G. Popovich, Yutaka Yoshida

    NATURE NEUROSCIENCE   19 ( 6 )   784 - +   2016.6

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

    DOI： 10.1038/nn.4289

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  • Bidirectional tuning of microglia in the developing brain: from neurogenesis to neural circuit formation Reviewed

    Masaki Ueno, Toshihide Yamashita

    CURRENT OPINION IN NEUROBIOLOGY   27   8 - 15   2014.8

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

    DOI： 10.1016/j.conb.2014.02.004

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  • A selector orchestrates cortical function Invited

    Masaki Ueno, Ryosuke Fujiki, Toshihide Yamashita

    NATURE NEUROSCIENCE   17 ( 8 )   1016 - 1017   2014.8

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  • ifn-gamma-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury Reviewed

    H. Ishii, S. Tanabe, M. Ueno, T. Kubo, H. Kayama, S. Serada, M. Fujimoto, K. Takeda, T. Naka, T. Yamashita

    CELL DEATH & DISEASE   4   e710   2013.7

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

    DOI： 10.1038/cddis.2013.234

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  • Layer v cortical neurons require microglial support for survival during postnatal development Reviewed

    Masaki Ueno, Yuki Fujita, Tatsuhide Tanaka, Yuka Nakamura, Junichi Kikuta, Masaru Ishii, Toshihide Yamashita

    Nature Neuroscience   16 ( 5 )   543 - 551   2013.5

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

    DOI： 10.1038/nn.3358

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  • Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury Reviewed

    T. Tanaka, Y. Fujita, M. Ueno, L. D. Shultz, T. Yamashita

    Cell Death and Disease   4 ( 4 )   e567   2013.4

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  • Bilateral movement training promotes axonal remodeling of the corticospinal tract and recovery of motor function following traumatic brain injury in mice Reviewed

    H. Nakagawa, M. Ueno, T. Itokazu, T. Yamashita

    CELL DEATH & DISEASE   4   e534   2013.3

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    DOI： 10.1038/cddis.2013.62

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  • Soluble β-amyloid Precursor Protein Alpha binds to p75 neurotrophin receptor to promote neurite outgrowth. Reviewed International journal

    Noriko Hasebe, Yuki Fujita, Masaki Ueno, Kazuhiro Yoshimura, Yuji Fujino, Toshihide Yamashita

    PloS one   8 ( 12 )   e82321   2013

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    BACKGROUND: The cleavage of β-amyloid precursor protein (APP) generates multiple proteins: Soluble β-amyloid Precursor Protein Alpha (sAPPα), sAPPβ, and amyloid β (Aβ). Previous studies have shown that sAPPα and sAPPβ possess neurotrophic properties, whereas Aβ is neurotoxic. However, the underlying mechanism of the opposing effects of APP fragments remains poorly understood. In this study, we have investigated the mechanism of sAPPα-mediated neurotrophic effects. sAPPα and sAPPβ interact with p75 neurotrophin receptor (p75(NTR)), and sAPPα promotes neurite outgrowth. METHODS AND FINDINGS: First, we investigated whether APP fragments interact with p75(NTR), because full-length APP and Aβ have been shown to interact with p75(NTR) in vitro. Both sAPPα and sAPPβ were co-immunoprecipitated with p75(NTR) and co-localized with p75(NTR) on COS-7 cells. The binding affinity of sAPPα and sAPPβ for p75(NTR) was confirmed by enzyme-linked immunosorbent assay (ELISA). Next, we investigated the effect of sAPPα on neurite outgrowth in mouse cortical neurons. Neurite outgrowth was promoted by sAPPα, but sAPPα was uneffective in a knockdown of p75(NTR). CONCLUSION: We conclude that p75(NTR) is the receptor for sAPPα to mediate neurotrophic effects.

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  • Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and functional recovery after spinal cord injury Reviewed

    H. Ishii, X. Jin, M. Ueno, S. Tanabe, T. Kubo, S. Serada, T. Naka, T. Yamashita

    CELL DEATH & DISEASE   3   e363   2012.8

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  • Intraspinal rewiring of the corticospinal tract requires target-derived brain-derived neurotrophic factor and compensates lost function after brain injury Reviewed

    Masaki Ueno, Yasufumi Hayano, Hiroshi Nakagawa, Toshihide Yamashita

    BRAIN   135 ( 4 )   1253 - 1267   2012.4

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  • c-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice. Reviewed International journal

    Kazuhiro Yoshimura, Masaki Ueno, Sachiko Lee, Yuka Nakamura, Akinobu Sato, Koichi Yoshimura, Haruhiko Kishima, Toshiki Yoshimine, Toshihide Yamashita

    Neuroscience research   71 ( 3 )   266 - 77   2011.11

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    c-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In Jnk1(-/-) and Jnk3(-/-) mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI.

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  • RhoA Activation and Effect of Rho-kinase Inhibitor in the Development of Retinal Neovascularization in a Mouse Model of Oxygen-induced Retinopathy Reviewed

    Xiaoyun Fang, Masaki Ueno, Toshihide Yamashita, Yasushi Ikuno

    CURRENT EYE RESEARCH   36 ( 11 )   1028 - 1036   2011.11

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    DOI： 10.3109/02713683.2011.593110

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  • Activated Microglia Inhibit Axonal Growth through RGMa Reviewed

    Mari Kitayama, Masaki Ueno, Toru Itakura, Toshihide Yamashita

    PLOS ONE   6 ( 9 )   e25234   2011.9

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  • Kinematic analyses reveal impaired locomotion following injury of the motor cortex in mice Reviewed

    Masaki Ueno, Toshihide Yamashita

    EXPERIMENTAL NEUROLOGY   230 ( 2 )   280 - 290   2011.8

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    DOI： 10.1016/j.expneurol.2011.05.006

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  • Corticospinal tract fibers cross the ephrin-B3-negative part of the midline of the spinal cord after brain injury Reviewed

    Shusaku Omoto, Masaki Ueno, Soichiro Mochio, Toshihide Yamashita

    NEUROSCIENCE RESEARCH   69 ( 3 )   187 - 195   2011.3

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    DOI： 10.1016/j.neures.2010.12.004

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  • Axonal remodeling for motor recovery after traumatic brain injury requires downregulation of gamma-aminobutyric acid signaling Reviewed

    S. Lee, M. Ueno, T. Yamashita

    CELL DEATH & DISEASE   2   e133   2011.3

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    DOI： 10.1038/cddis.2011.16

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  • Dynamic Spatiotemporal Gene Expression in Embryonic Mouse Thalamus Reviewed

    Asuka Suzuki-Hirano, Masaharu Ogawa, Ayane Kataoka, Aya C. Yoshida, Daisuke Itoh, Masaki Ueno, Seth Blackshaw, Tomomi Shimogori

    JOURNAL OF COMPARATIVE NEUROLOGY   519 ( 3 )   528 - 543   2011.2

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    DOI： 10.1002/cne.22531

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  • Paired Immunoglobulin-like Receptor B Knockout Does Not Enhance Axonal Regeneration or Locomotor Recovery after Spinal Cord Injury Reviewed

    Yuka Nakamura, Yuki Fujita, Masaki Ueno, Toshiyuki Takai, Toshihide Yamashita

    JOURNAL OF BIOLOGICAL CHEMISTRY   286 ( 3 )   1876 - 1883   2011.1

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    DOI： 10.1074/jbc.M110.163493

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  • Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury Reviewed

    Shusaku Omoto, Masaki Ueno, Soichiro Mochio, Toshiyuki Takai, Toshihide Yamashita

    JOURNAL OF NEUROSCIENCE   30 ( 39 )   13045 - 13052   2010.9

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    DOI： 10.1523/JNEUROSCI.3228-10.2010

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  • Olfactory Mucosal Transplantation After Spinal Cord Injury Improves Voiding Efficiency by Suppressing Detrusor-Sphincter Dyssynergia in Rats Reviewed

    Jiro Nakayama, Tetsuya Takao, Hiroshi Kiuchi, Keisuke Yamamoto, Shinichiro Fukuhara, Yasushi Miyagawa, Masanori Aoki, Koichi Iwatsuki, Toshiki Yoshimine, Masaki Ueno, Toshihide Yamashita, Norio Nonomura, Akira Tsujimura, Akihiko Okuyama

    JOURNAL OF UROLOGY   184 ( 2 )   775 - 782   2010.8

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    DOI： 10.1016/j.juro.2010.03.105

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  • Expression of galectin-1 in immune cells and glial cells after spinal cord injury Reviewed

    Dai Kurihara, Masaki Ueno, Tatsuhide Tanaka, Toshihide Yamashita

    NEUROSCIENCE RESEARCH   66 ( 3 )   265 - 270   2010.3

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  • Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa: laboratory investigation. Reviewed International journal

    Masanori Aoki, Haruhiko Kishima, Kazuhiro Yoshimura, Masahiro Ishihara, Masaki Ueno, Katsuhiko Hata, Toshihide Yamashita, Koichi Iwatsuki, Toshiki Yoshimine

    Journal of neurosurgery. Spine   12 ( 2 )   122 - 30   2010.2

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    OBJECT: The olfactory mucosa (OM) consists of 2 layers, the epithelium and the lamina propria. Attempts have been made to restore motor function in rat models of spinal cord injury (SCI) by transplanting olfactory ensheathing cells from the lamina propria, but there has been no attempt to transplant the OM in animal models. To investigate the potential of the OM to restore motor function, the authors developed a rat model of SCI and delayed transplantation of syngenic OM. METHODS: Two weeks after complete transection of the spinal cord at the T-10 level in Wistar rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats that underwent respiratory mucosa transplantation were used as controls. The authors evaluated the locomotor activity according to the Basso-Beattie-Bresnahan scale for 8 weeks after transplantation. Obtained spinal cords were analyzed histologically. Results The OM transplantation rats showed significantly greater hindlimb locomotor recovery than the respiratory mucosa-transplanted rats. However, the recovery was limited according to the Basso-Beattie-Bresnahan scale. In the histological examination, the serotonergic raphespinal tract was regenerated. The pseudocyst cavity volume in the vicinity of the SCI lesion correlated negatively with the functional recovery. CONCLUSIONS: Transplantation of whole-layer OM in rats contributes to functional recovery from SCI, but the effect is limited. In addition to OM transplantation, other means would be necessary for better outcomes in clinical situations.

    DOI： 10.3171/2009.9.SPINE09233

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  • Engulfment of Axon Debris by Microglia Requires p38 MAPK Activity Reviewed

    Tatsuhide Tanaka, Masaki Ueno, Toshihide Yamashita

    JOURNAL OF BIOLOGICAL CHEMISTRY   284 ( 32 )   21626 - 21636   2009.8

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    DOI： 10.1074/jbc.M109.005603

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  • Etoposide Induces TRP53-Dependent Apoptosis and TRP53-Independent Cell Cycle Arrest in Trophoblasts of the Developing Mouse Placenta Reviewed

    Hirofumi Yamauchi, Kei-ichi Katayama, Masaki Ueno, Hiroyuki Kanemitsu, Chunja Nam, Takashi Mikami, Aya Saito, Yuka Ishida, Koji Uetsuka, Kunio Doi, Yasushi Ohmach, Hiroyuki Nakayama

    BIOLOGY OF REPRODUCTION   80 ( 4 )   813 - 822   2009.4

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    DOI： 10.1095/biolreprod.108.069419

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  • Intrinsic regenerative mechanisms of central nervous system neurons Reviewed

    Rieko Muramatsu, Masaki Ueno, Toshihide Yamashita

    BIOSCIENCE TRENDS   3 ( 5 )   179 - 183   2009

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  • Regulation of axonal elongation and pathfinding from the entorhinal cortex to the dentate gyrus in the hippocampus by the chemokine stromal cell-derived factor 1 alpha Reviewed

    Yoichi Ohshima, Takekazu Kubo, Ryuta Koyama, Masaki Ueno, Masanori Nakagawa, Toshihide Yamashita

    JOURNAL OF NEUROSCIENCE   28 ( 33 )   8344 - 8353   2008.8

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    DOI： 10.1523/JNEUROSCI.1670-08.2008

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  • Strategies for regenerating injured axons after spinal cord injury - insights from brain development. Reviewed

    Masaki Ueno, Toshihide Yamashita

    Biologics : targets & therapy   2   253 - 264   2008.6

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    Axonal regeneration does not occur easily after an adult central nervous system (CNS) injury. Various attempts have partially succeeded in promoting axonal regeneration after the spinal cord injury (SCI). Interestingly, several recent therapeutic concepts have emerged from or been tightly linked to the researches on brain development. In a developing brain, remarkable and dynamic axonal elongation and sprouting occur even after the injury; this finding is essential to the development of a therapy for SCI. In this review, we overview the revealed mechanism of axonal tract formation and plasticity in the developing brain and compare the differences between a developing brain and a lesion site in an adult brain. One of the differences is that mature glial cells participate in the repair process in the case of adult injuries. Interestingly, these cells express inhibitory molecules that impede axonal regeneration such as myelin-associated proteins and the repulsive guidance molecules found originally in the developing brain for navigating axons to specific routes. Some reports have clearly elucidated that any treatment designed to suppress these inhibitory cues is beneficial for promoting regeneration and plasticity after an injury. Thus, understanding the developmental process will provide us with an important clue for designing therapeutic strategies for recovery from SCI.

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  • Gene expression profiles of drug-metabolizing enzymes (DMEs) in rat liver during pregnancy and lactation Reviewed

    Xi Jun He, Hirofumi Yamauchi, Kazuhiko Suzuki, Masaki Ueno, Hiroyuki Nakayama, Kunio Doi

    EXPERIMENTAL AND MOLECULAR PATHOLOGY   83 ( 3 )   428 - 434   2007.12

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    DOI： 10.1016/j.yexmp.2006.05.002

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  • Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent Reviewed

    Hirofumi Yamauchi, Kei-ichi Katayama, Masaki Ueno, Xi Jun He, Takashi Mikami, Koji Uetsuka, Kunio Doi, Hiroyuki Nakayama

    APOPTOSIS   12 ( 10 )   1743 - 1754   2007.10

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    DOI： 10.1007/s10495-007-0099-z

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  • Repair process of fetal brain after 5-azacytidine-induced damage Reviewed

    Masaki Ueno, Kei-ichi Katayama, Hirofumi Yamauchi, Akira Yasoshima, Hiroyuki Nakayama, Kunio Doi

    EUROPEAN JOURNAL OF NEUROSCIENCE   24 ( 10 )   2758 - 2768   2006.11

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    DOI： 10.1111/j.1460-9568.2006.05161.x

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  • Evidence of apoptosis in the subventricular zone and rostral migratory stream in the MPTP mouse model of Parkinson disease Reviewed

    Xi Jun He, Hiroyuki Nakayama, Mei Dong, Hirofumi Yamauchi, Masaki Ueno, Koji Uetsuka, Kunio Doi

    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY   65 ( 9 )   873 - 882   2006.9

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    DOI： 10.1097/01.jnen.0000235115.29440.ce

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  • Cell cycle progression is required for nuclear migration of neural progenitor cells Reviewed

    M Ueno, K Katayama, H Yamauchi, H Nakayama, K Doi

    BRAIN RESEARCH   1088   57 - 67   2006.5

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    DOI： 10.1016/j.brainres.2006.03.042

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  • Cell cycle and cell death regulation of neural progenitor cells in the 5-azacytidine (5AzC)-treated developing fetal brain Reviewed

    M Ueno, K Katayama, H Yamauchi, H Nakayama, K Doi

    EXPERIMENTAL NEUROLOGY   198 ( 1 )   154 - 166   2006.3

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    DOI： 10.1016/j.expneurol.2005.11.024

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  • Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration Reviewed

    K Katayama, M Ueno, H Yamauchi, H Nakayama, K Doi

    BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY   74 ( 3 )   255 - 260   2005.6

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    DOI： 10.1002/bdrb.20045

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  • Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner Reviewed

    K Katayama, M Ueno, H Yamauchi, T Nagata, H Nakayama, K Doi

    NEUROBIOLOGY OF DISEASE   18 ( 1 )   218 - 225   2005.2

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    DOI： 10.1016/j.nbd.2004.09.015

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  • Effects of prenatal hydroxyurea-treatment on mouse offspring Reviewed

    GH Woo, K Katayama, EJ Bak, M Ueno, H Yamauchi, K Uetsuka, H Nakayama, K Doi

    EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY   56 ( 1-2 )   1 - 7   2004.10

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    DOI： 10.1016/j.etp.2004.04.011

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  • Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced rat fetal brain lesions Reviewed

    H Yamauchi, K Katayama, M Ueno, K Uetsuka, H Nakayama, K Doi

    NEUROTOXICOLOGY AND TERATOLOGY   26 ( 4 )   579 - 586   2004.7

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    DOI： 10.1016/j.ntt.2004.03.010

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  • Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta Reviewed

    H Yamauchi, K Katayama, M Ueno, K Uetsuka, H Nakayama, K Doi

    BIOLOGY OF REPRODUCTION   70 ( 6 )   1762 - 1767   2004.6

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    DOI： 10.1095/biolreprod.103.026252

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  • Age-dependent susceptibility to MPTP neurotoxicity in C57BL mice: A tyrosine hydroxylase-immunohistochemical evaluation Reviewed

    Xi Jun He, Hiroyuki Nakayama, Masaki Ueno, Kunio Doi

    Journal of Toxicologic Pathology   17 ( 4 )   239 - 244   2004

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    DOI： 10.1293/tox.17.239

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  • Ethylnitrosourea-induced apoptosis in primordial germ cells of the rat fetus Reviewed

    K Katayama, M Ueno, H Yamauchi, H Nakayama, K Doi

    EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY   54 ( 3 )   193 - 196   2002.11

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  • 5-azacytidine (5AzC)-induced histopathological changes in the central nervous system of rat fetuses Reviewed

    M Ueno, K Katayama, A Yasoshima, H Nakayama, K Doi

    EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY   54 ( 2 )   91 - 96   2002.8

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  • Ethylnitrosourea induces apoptosis and growth arrest in the trophoblastic cells of rat placenta Reviewed

    K Katayama, M Ueno, H Takai, N Ejiri, K Uetsuka, H Nakayama, K Doi

    BIOLOGY OF REPRODUCTION   67 ( 2 )   431 - 435   2002.8

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  • Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain Reviewed

    M Ueno, KI Katayama, H Nakayama, K Doi

    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY   83 ( 3 )   139 - 150   2002.6

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    DOI： 10.1046/j.1365-2613.2002.00225.x

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  • Expression of ribosomal protein L4 (rpL4) during neurogenesis and 5-azacytidine (5AzC)-induced apoptotic process in the rat Reviewed

    Masaki Ueno, H. Nakayama, S. Kajikawa, K. Katayama, K. Suzuki, K. Doi

    Histology and Histopathology   17 ( 3 )   789 - 798   2002

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MISC

  • Approaches for inducing neural plasticity via targeting inhibitory circuits after stroke Invited

    Inoue T., Ueno M.

    Medical Science Digest   51 ( 7 )   74 - 76   2025.6

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  • Elucidating the neural network of cerebrospinal fluid-contacting neurons Invited

    Yuka Nakamura, Masaki Ueno

    Seitai No Kagaku   75 ( 5 )   406 - 407   2024.10

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  • Rehabilitation to restore neural repair capacity in the aged brain. Invited

    Tanaka T, Ueno M

    Medical Science Digest   50 ( 12 )   602 - 604   2024.10

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  • Protein spreading in ALS: disease progression by TDP-43 in the motor circuits Invited

    Tsuboguchi S, Onodera O, Ueno M

    Farumashia   60 ( 5 )   393 - 397   2024.5

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  • Rewiring of the corticospinal circuit and the molecular mechanism after stroke Invited

    Sato T, Ueno M

    Medical Science Digest   50 ( 6 )   48 - 50   2024.5

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  • Autonomic dysfunction and neural circuit rewiring in spinal cord injury Invited Reviewed

    Ueno M

    The Autonomic Nervous System   60 ( 3 )   110 - 114   2023.9

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  • Voluntary running restores age-related loss of neural repair abitlities and circadian rhythms after brain injury. Invited Reviewed

    Tanaka T, Ura H, Maeda T, Yanagita N, Mitsugi K, Koki H, Ueno M

    J Phys Ther Fund   advpub   2023.7

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    Brain injury often causes severe motor dysfunction. Previously, we showed that the corticospinal tract (CST) axons are rewired to form an intraspinal circuit that contributes to motor recovery after brain injury in young adult mice. Although brain injury is often suffered by elderly individuals, little is known about the ability of rewiring and functional recovery in aged rodent model. In this study, we examined CST sprouting and functional recovery in aged mice after brain injury and further investigated whether voluntary running could promote them. We found that axon sprouting was limited and motor function was not recovered in aged mice. Contrastingly, voluntary running significantly increased sprouting and enhanced motor recovery. Moreover, we performed RNA sequencing to examine exercise-induced gene expression of motor area changes in aged mice. Expressions of 91 genes increased in exercised aged mice compared to non-exercised mice, in which a set of circadian rhythm-related genes was involved. Accordingly, a day-night activity rhythm was impaired in the aged mice, whereas it was gradually recovered by exercise, similar to the patterns of younger mice. Our study reveals that voluntary running restores circadian rhythms, CST sprouting, and motor recovery after brain injury in aged mice.

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  • 脳脊髄液接触ニューロン 脳脊髄液センサーとしての可能性を探る Invited

    中村 由香, 上野 将紀

    細胞   55 ( 5 )   308 - 312   2023.4

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  • 中枢神経の障害にともなう皮質脊髄路の再編 Invited

    井上 貴博, 上野 将紀

    神経心理学   39 ( 1 )   30 - 39   2023.3

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  • リハビリテーションと分子標的の併用による脳損傷後の機能回復 Invited

    田中 貴士, 上野 将紀

    基礎理学療法学   25 ( 1 )   43 - 49   2022.10

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  • 脳・脊髄障害後の神経回路再編の可視化 Invited

    佐藤時春, 上野将紀

    Clinical Neuroscience   40 ( 6 )   746 - 749   2022.6

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    Authorship：Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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  • Immune deficiency and pathology in CNS injuries. Invited

    Masaki Ueno

    Seitai No Kagaku   72 ( 5 )   409 - 411   2021.10

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    Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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  • Immune deficiency in the central nervous system injury. Invited

    Ueno M

    J Clin Exp Med (Igaku No Ayumi)   277 ( 13 )   1104 - 1107   2021.6

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    Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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  • Restoring neural circuits and functions after CNS injuries. Invited

    Ueno M

    Niigata Med J   134 ( 1 )   7 - 12   2020.12

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    Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

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  • Reconstruction of neural circuits for voluntary movements –perspectives in basic research– Invited

    Masaki Ueno

    J Niigata Med Assoc   842   2 - 7   2020.5

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    Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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  • Mechanisms and mystery of motor behavior Invited

    Masaki Ueno

    Nouken Column   2020.3

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    Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (other)  

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  • Brain, organs, and immune interaction in spinal cord injury. Invited

    Masaki Ueno

    Experimental Medicine (Jikken Igaku)   36 ( 3 )   370 - 376   2019.7

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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  • Brain-immune interaction in CNS injuries. Invited

    Masaki Ueno

    Experimental Medicine (Jikken Igaku)   36 ( 3 )   370 - 376   2018.1

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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  • Microglia in brain development Invited

    Masaki Ueno

    Brain and Nerve   69 ( 9 )   985 - 997   2017.9

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：Igaku-Shoin Ltd  

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  • Rewiring of neural circuits and functional recovery following brain and spinal cord injuries. Invited Reviewed

    Masaki Ueno

    Lifescience Ryoiki Yugo Review   6   e003   2017.6

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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  • Rewiring of sympathetic circuitry and immune suppression after spinal cord injury Invited

    Ueno M, Popovich PG, Yoshida Y

    Experimental Medicine (Jikken Igaku)   34 ( 14 )   2328 - 2331   2016.8

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  • The brain immune network in spinal cord injury Invited

    Masaki Ueno, Toshihide Yamashita

    Neurodegenerative Disorders as Systemic Diseases   41 - 66   2015.1

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    Language：English   Publisher：Springer Japan  

    DOI： 10.1007/978-4-431-54541-5_3

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  • Layer v cortical neurons require microglial support for survival during postnatal development

    Masaki Ueno, Yuki Fujita, Tatsuhide Tanaka, Yuka Nakamura, Junichi Kikuta, Masaru Ishii, Toshihide Yamashita

    Nature Neuroscience   16 ( 5 )   543 - 551   2013.5

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  • 研コミュ白書 第9回 UC-Tomorrow: シンシナティから発する明日のサイエンスへの光ー遥かなる上を目指してー

    山田宗茂, 合山進, 上野将紀, 佐々木敦朗

    細胞工学   32 ( 11 )   1174 - 1177   2013

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    Language：Japanese   Publisher：学研メディカル秀潤社 ; 1982-  

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▶ display all

Research Projects

  • Manipulating Descending Pain Suppression Systems Using Chemogenetics to Find Seeds for Chronic Pain Treatment

    Grant number：22H03167

    2022.4 - 2026.3

    System name：Grants-in-Aid for Scientific Research

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

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\16510000 （ Direct Cost: \12700000 、 Indirect Cost：\3810000 ）

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  • リハビリテーションが誘導する障害後の皮質脊髄路可塑性の分子基盤の解明

    Grant number：21H05683

    2021.9 - 2023.3

    System name：科学研究費助成事業

    Research category：学術変革領域研究(A)

    Awarding organization：日本学術振興会

    上野 将紀

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    Grant amount：\7800000 （ Direct Cost: \6000000 、 Indirect Cost：\1800000 ）

    リハビリテーションは、中枢神経障害後の機能回復の促進に広く用いられ、回路の可塑性と再編がその機序の根幹に存在することが示唆されている。しかし、リハビリテーションがどのように可塑性を高め、回路再編と機能回復を促すのか、その神経・分子基盤の理解は進んでいない。本研究では、運動によるリハビリテーションが、脳障害後に可塑性を誘導し、随意運動を担う皮質脊髄路の再編を引き起こすメカニズムを明らかにすることで、リハビリテーションによる回路再編と機能回復の分子神経基盤を解明することを目的とする。本年度はまず、Rose Bengalを用いた光血栓形成により、大脳皮質に梗塞を起こす脳障害モデルを確立し、残存した皮質脊髄路の回路網における再編様式の挙動を解析した。まず大脳皮質の各領野特異的に梗塞が起こった場合の再編様式を探索したところ、脳梗塞の起こる部位により皮質脊髄路が異なる様式で再編することが明らかとなった。さらに運動を一定時間行わせるリハビリテーションにより、脳梗塞後、皮質脊髄路の再編が促進されるかを解剖学的に解析した。その結果、運動リハビリテーションにより皮質脊髄路の軸索の伸長が増加し、再編が促進されることがわかった。さらに脳梗塞後、再編する回路網において誘導される遺伝子発現の変動を調べた。その結果、梗塞後、経時的に変動する遺伝子発現のデータを取得することができた。得られた成果は、リハビリテーションによる皮質脊髄路の再編機序の理解へつながるものと期待される。

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  • Application of the Autonomic Nervous Management for NAFLD Treatment

    Grant number：21K19478

    2021.7 - 2024.3

    System name：Grants-in-Aid for Scientific Research

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

    Awarding organization：Japan Society for the Promotion of Science

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

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  • 脳内修復におけるミクログリアによるタウ排泄機序の解明

    Grant number：21K19441

    2021.7 - 2024.3

    System name：科学研究費助成事業

    Research category：挑戦的研究(萌芽)

    Awarding organization：日本学術振興会

    金澤 雅人, 田井中 一貴, 清水 宏, 上野 将紀

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    Grant amount：\6240000 （ Direct Cost: \4800000 、 Indirect Cost：\1440000 ）

    認知症の原因となるタウ蛋白蓄積が生じる能血管障害モデルをもとに，タウ蓄積とその排泄に関して機序の解明を行う．脳血管障害に伴うタウ蛋白蓄積を解明することのみならず，その障害の基盤を解明する研究である．ミクログリアで，タウ蓄積を軽減し，認知機能を改善することができれば，高血圧，糖尿病，高脂血症治療薬を用いて，ミクログリアを保護的に修飾し，タウ排泄促進するかを検討する．これにて，ドラッグ・リポジショニングの応用が可能である．さらに，異常蛋白蓄積による神経変性疾患にも応用可能な提案であり，他の蛋白排泄機序の解明につながり，他の神経疾患研究にも展開する．

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  • 脳-脊髄をつなぐ運動性下行路再編の統合的解析

    Grant number：21H02590

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    上野 将紀

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

    本研究では、脳障害後におこる、脳－脊髄をつなぐ運動下行路の再編様式を明らかにし、障害部位別に起こる再編のパターンとその機能を体系化することを目的とする。脳の障害は、神経回路を破綻させ、運動をはじめとする神経機能の低下をもたらす。一方、失われた機能は、自然回復あるいは増悪したりと変容することが知られ、この機能の変化は、障害から逃れ残存した神経回路の可塑的、代償的な変化により起こると近年示されている。申請者はこれまで、脳障害後に運動機能を担う下行路の１つである皮質脊髄路が再編することを見出し、残された神経の可塑的変化が、機能の回復を導く鍵となる現象であると示してきた。適切な回路の可塑性を増強し治療標的とするには、多様な脳障害部位に応じて再編し機能回復をもたらす神経回路の局在やその挙動の理解が求められており、本研究ではその体系化を試みる。本年度は、光血栓形成により任意の大脳皮質領域に梗塞を引き起こすモデルを確立し、障害を逃れた大脳皮質の残存領域から伸びる皮質脊髄路が脊髄で再編する様式の変化を解析した。これまでマウスでは、頸髄に投射する皮質脊髄路ニューロンは大脳皮質の大きく３ヶ所 (運動野（CFA，RFA），感覚野S1)に分布することを見出していることから、この各脳領域が障害されるモデルを確立した。これらのモデルのうち、広範に脳梗塞を起こした場合には、障害対側の皮質脊髄路が頸髄において出芽・伸長して再編することがわかった。一方、やや小型の脳梗塞（RFA+S1領域）を起こした場合には、障害同側の皮質脊髄路が再編することがわかった。さらに、見出した再編軸索の接続や機能を解析する実験にも取り組み、その接続様式や機能が見えはじめた。得られた成果は、脳障害後におこる運動下行路の再編様式と機序の理解へつながるものと期待される。

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  • 光遺伝学を利用した青斑核ニューロン制御による全身麻酔薬作用機序の解明

    Grant number：21K08943

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    倉部 美起, 佐々木 美佳, 上野 将紀

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

    全身麻酔薬の作用機序は現代においても未解明である。睡眠・覚醒と密接な関わりを持つ、“青斑核”を起始核とするノルアドレナリン（NA）ニューロンが全身麻酔時の意識消失や覚醒にも関与していると考えられているが、詳細は不明である。近年、青斑核ニューロンが一様ではなく、NAニューロン以外にGABA（gamma-Aminobutyric acid）ニューロンを含み、相互作用していることが明らかになったことから、GABAニューロンとNAニューロンとの相互の関係性が、全身麻酔薬の作用機序に大きく関与しているのではないかと考えた。そこで、全身麻酔時の青斑核NA/GABAニューロンの活動が果たす機能的役割とそれぞれの神経の相互関連性を、光遺伝学的手法を用いて解明することを目的とした。
    初年度は光遺伝学的手法の導入と確認を組織学的・生理学的両面から行った。青斑核NAニューロンを特異的に操作するために、NAニューロン特異的プロモーターPRSx8下でチャネルロドプシン・アーキロドプシンを発現するアデノ随伴ウイルスを作製し、C57BL/6マウス青斑核に脳定位固定装置を用いて投与した。免疫組織学的に、青斑核ニューロンに特異的に発現することを確認した。さらにこれらのマウスから青斑核スライス標本を作製し近赤外線
    微分干渉顕微鏡を用いて可視下にホールセルパッチクランプ記録を行った。NAニューロンは電流固定モード下で３～４Hzの活動電位を発していた。また、光刺激によって活動電位の発火頻度が増加あるいは減少することを確認した。
    これらの結果を基に、次年度はNA/GABAニューロン制御下に電気生理学解析を進め、無麻酔状態のマウスからの脳波・行動解析を行う予定である。

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  • 脳脊髄液を探知する神経回路の機能の解明

    Grant number：20K21460

    2020.7 - 2023.3

    System name：科学研究費助成事業

    Research category：挑戦的研究(萌芽)

    Awarding organization：日本学術振興会

    上野 将紀

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

    本研究では、脳脊髄液に接する未知の細胞である脳脊髄液接触ニューロンのもつ細胞構造や神経回路網、機能の解明を目的に研究を進めている。本細胞は、脳脊髄液と接する特徴的な構造を有することから、脳内外の生体環境の情報を有する脳脊髄液の情報を感知し、中枢神経系の神経回路内へ伝達する重要な細胞群であることが想定される。しかし、その機能や実体はほとんどわかっていないのが現状である。本年度は、前年度までに確立した同ニューロンを蛍光標識などで可視化する方法を用いて、同ニューロンが構成している神経回路網の様式を解明する研究に取り組んだ。各種の遺伝子改変マウスや神経トレーサーを駆使して、多様に存在する脊髄ニューロン種との接続様式の解析を進めた。解剖・組織学的な実験を進めた結果、同ニューロンは、特定の脊髄ニューロンとシナプス接続をしている可能性を見出した。一部の接続は、電子顕微鏡を用いた観察によっても確かめられた。次に、同ニューロンやその回路網が持っている機能を探索する研究への展開を試みた。そのため、同ニューロンの選択的な除去や神経活動の操作をすることにより、機能を特異的に阻害する方法の検討を行った。検討を行った中、一部の方法を用いることにより、同ニューロンの機能を阻害できる可能性を見出した。この方法論は、同ニューロンの機能の解明を目指した研究へ有用になると考えられる。ここで得られた成果は、生体-神経をつなぐ新たな細胞・生体メカニズムの理解へ貢献すると期待される。

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  • 高齢期の認知機能におけるチロシン脱リン酸化酵素SHP-1の機能解析

    Grant number：20K11222

    2020.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    田中 貴士, 加藤 伸郎, 上野 将紀

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    アルツハイマー型認知症に対する有効な治療法は未だ確立されていない。認知症の改善のためには、海馬における神経新生を増加させること、脳に蓄積したアミロイドβなどの代謝廃棄物の除去を促すこと、の２点が重要である。本研究で着目しているチロシン脱リン酸化酵素（SHP-1）は、神経新生やミクログリアによる代謝廃棄物の貪食を阻害することが報告されている。そこで、SHP-1の抑制がアルツハイマー病の予防・改善に有効であるのではないかと仮説を立て、研究を進めている。
    本研究で用いるアルツハイマー型認知症マウスは、成長早期から脳内にアミロイドβの顕著な蓄積がみられ、認知症を示すマウスである。アルツハイマー型認知症マウスとSHP-1欠損マウスを交配させることで、SHP-1が減少したアルツハイマー型認知症マウスを作製し、20月齢まで成長させた。このマウスにおいて、脳内のアミロイドβの蓄積をタンパク質及び組織学的に解析した結果、特に海馬におけるアミロイドβの蓄積が緩和され、認知機能の低下が改善されるデータを積み重ねることができている。また、SHP-1欠損のアルツハイマー型認知症マウスの海馬における神経新生の評価を開始しており、統計学的な解析を進めているところである。

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  • Elucidating mechanisms of action of general anesthetics using chemogenetics

    Grant number：19K22652

    2019.6 - 2022.3

    System name：Grants-in-Aid for Scientific Research

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

    Awarding organization：Japan Society for the Promotion of Science

    Kamiya Yoshinori

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    Grant amount：\6240000 （ Direct Cost: \4800000 、 Indirect Cost：\1440000 ）

    The purpose of this study was to use chemogenetics to manipulate noradrenergic (NA) neurons in the locus coeruleus to determine the role of NA neurons in the loss of consciousness and arousal during general anesthesia. To specifically manipulate the NA neurons, an adeno-associated virus (AAV1-PRSx8-hM3Dq-HA) was prepared and injected into the rat locus coeruleus. NA neuron activation only slightly altered the induction and arousal times of volatile anesthetics, but markedly altered the induction and arousal times of intravenous anesthetics. Furthermore, we established a method for electrophysiological analysis under free moving and under the control of the NA neurons

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  • Effect of Organ Communication on Liver Function upon the Liver Injury

    Grant number：18K19537

    2018.6 - 2020.3

    System name：Grants-in-Aid for Scientific Research

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

    Awarding organization：Japan Society for the Promotion of Science

    Shuji Terai

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    Grant amount：\6240000 （ Direct Cost: \4800000 、 Indirect Cost：\1440000 ）

    The development of therapeutic options to promote hepatic is essential. While humoral factors have been reported as mechanisms of liver regeneration, the contributions of inter-organ communication to liver regeneration have not been reported. Therefore, in this study, we examined the effect of neural relay on liver regeneration via activation of gastrointestinal hormone release from the gastrointestinal tract. Our results demonstrated that the afferent visceral nerve from the liver activates the efferent vagus nerve from the brain, leading to activation of hormone release from the gastrointestinal tract and contributing to the liver regeneration.

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  • Development of tools to analyze neuronal functional modules in the brain

    Grant number：17K19443

    2017.6 - 2021.3

    System name：Grants-in-Aid for Scientific Research

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

    Awarding organization：Japan Society for the Promotion of Science

    Ueno Masaki

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

    This study is aimed to develop a variety of tools to analyze the connection patterns and functions of specific neural circuit in the central nervous system. We developed various tools to label synapses, intracellular organelles or a single soma, to detect or manipulate neural activities, to analyze functions of expressed molecules, and to remove neurons, in specific neuronal subtypes of the mouse brain. The library of developed tools enables labeling and manipulation of target neurons and will contribute to elucidate the connectivity and functions of specific neural circuits in the central nervous system.

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  • Elucidating the mechanisms underlying the neural circuit reorganization after brain injuries

    Grant number：17H04985

    2017.4 - 2021.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Young Scientists (A)

    Awarding organization：Japan Society for the Promotion of Science

    Ueno Masaki

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    Grant amount：\23660000 （ Direct Cost: \18200000 、 Indirect Cost：\5460000 ）

    Rewiring of neural circuits is one of the key processes to promote functional recovery after brain injuries. However, the mechanisms underlying the rewiring are not fully understood. The aim of this study is to reveal the structures and functions of rewired circuits, and the mechanism of rewiring after the injury. In particular, we examined the structures and functions of corticospinal circuit, the main neural pathway for voluntary movement, in control and injured brain. We first found that the corticospinal circuit consists of multiple pathways and connections, and each has distinct sensorimotor function. After the injury, we examined the degree and patterns of rewiring, and found several molecules and methods to promote axonal growth. Our data will contribute to understand the mechanism of neural reorganization and develop novel strategies to restore neural network and functions after the injuries.

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  • 脳障害後の神経回路再編促進モデルによる回路シフトの解析

    Grant number：17H05556

    2017.4 - 2019.3

    System name：科学研究費助成事業

    Research category：新学術領域研究(研究領域提案型)

    Awarding organization：日本学術振興会

    上野 将紀

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    Grant amount：\7020000 （ Direct Cost: \5400000 、 Indirect Cost：\1620000 ）

    脳において神経の軸索の伸長や再生が起こりにくい大きな要因に、①軸索の周囲環境に存在する軸索伸長阻害因子（外的要因）、②軸索伸長をうながす神経細胞内シグナルの枯渇（内的要因）、の２つが示されている。本研究では、これらの外的、内的要因を取り除くことが可能な遺伝子改変マウスによって、障害後の運動回路の再編や機能の回復を促進することができるか検証することを目的とする。特に、大脳皮質と脊髄をつなぎ自発的あるいは巧緻的な運動に必要とされる皮質脊髄路をターゲットとする。本年度は、外的、内的要因を標的としたシングル、ダブル、トリプルノックアウトマウスにおいて、皮質脊髄路の再編が促されるかどうかを検証するため、脊髄損傷モデルを構築した。皮質脊髄路の軸索を順行性神経トレーサーでラベルし、損傷後の軸索の伸長や退縮の度合いを評価した。その結果、外的要因を阻害したマウスでは、損傷による切断後の軸索の退縮が顕著に抑制された。一方、内的要因を克服したマウスでは、損傷による切断後の軸索の伸長が顕著に増加した。こうした変化が、回路の再編を促進するかを明らかにするため、経シナプス逆行性ウイルストレーサーを用いて、神経回路の接続解析を行った。その結果、これらのダブルノックアウトマウスにおいて、筋と大脳皮質を結ぶ回路の再編が増えることが明らかとなった。本研究の結果から、外的、内的要因は、神経回路の再生を阻む異なる過程に関わっていることがわかった。さらにこれらの要因を阻害することで、神経回路の再編を促進することが可能であることが示された。本研究の成果は、脳脊髄の障害に対し、外的、内的要因双方を標的として、機能回復をもたらす治療法の開発に貢献すると期待される。

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  • Disruption and recovery of homeostasis by neural network after CNS injury

    2013.10 - 2017.3

    System name：PRESTO

    Awarding organization：JST

    Masaki Ueno

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    Authorship：Principal investigator  Grant type：Competitive

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  • Mechanism of compensatory neural network formation after brain injury

    Grant number：21700381

    2009.4 - 2011.3

    System name：KAKENHI (Grant-in-Aid for Young Scientists (B))

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：MEXT

    Masaki Ueno

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    Authorship：Principal investigator  Grant type：Competitive

    Brain injury that results in an initial behavioral deficit is frequently followed by spontaneous functional recovery. In the present study, we showed that reorganization of the remnant neural network was crucial for spontaneous recovery of motor function following brain injury in mice. Furthermore, we identified several key signals (BDNF-TrkB, GABA, EphA4-EphrinB3, MAG/Nogo/OMgp-PirB) that modify this new network formation.

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Teaching Experience

  • 先端医科学研究概説

    2023
    Institution name：新潟大学