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  1. Article ; Online: Monosynaptic rabies virus tracing from projection-targeted single neurons.

    Masaki, Yuji / Yamaguchi, Masahiro / Takeuchi, Ryosuke F / Osakada, Fumitaka

    Neuroscience research

    2022  Volume 178, Page(s) 20–32

    Abstract: A single neuron integrates inputs from thousands of presynaptic neurons to generate outputs. Circuit tracing using G-deleted rabies virus (RVΔG) vectors permits the brain-wide labeling of presynaptic inputs to targeted single neurons. However, the ... ...

    Abstract A single neuron integrates inputs from thousands of presynaptic neurons to generate outputs. Circuit tracing using G-deleted rabies virus (RVΔG) vectors permits the brain-wide labeling of presynaptic inputs to targeted single neurons. However, the experimental procedures are complex, and the success rate of circuit labeling is low because of the lack of validation to increase the accuracy and efficiency of monosynaptic RVΔG tracing from targeted single neurons. We established an efficient RVΔG tracing method from projection target-defined single neurons using TVA950, a transmembrane isoform of TVA receptors, for initial viral infection. Presynaptic neurons were transsynaptically labeled from 80 % of the TVA950-expressing single starter neurons that survived after infection with EnvA-pseudotyped RVΔG in the adult mouse brain. We labeled single neuronal networks in the primary visual cortex (V1) and higher visual areas, namely the posteromedial area (PM) and anteromedial area (AM), as well as the single neuronal networks of PM-projecting V1 single neurons. Monosynaptic RVΔG tracing from projection-targeted single neurons revealed the input-output organization of single neuronal networks. Single-neuron network analysis based on RVΔG tracing will help dissect the heterogeneity of neural circuits and link circuit motifs and large-scale networks across scales, thereby clarifying information processing and circuit computation in the brain.
    MeSH term(s) Animals ; Brain ; Interneurons ; Mice ; Neurons/physiology ; Rabies virus
    Language English
    Publishing date 2022-01-31
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 605842-5
    ISSN 1872-8111 ; 0168-0102 ; 0921-8696
    ISSN (online) 1872-8111
    ISSN 0168-0102 ; 0921-8696
    DOI 10.1016/j.neures.2022.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Temporally multiplexed dual-plane imaging of neural activity with four-dimensional precision.

    Onda, Masanari / Takeuchi, Ryosuke F / Isobe, Keisuke / Suzuki, Toshiaki / Masaki, Yuji / Morimoto, Nao / Osakada, Fumitaka

    Neuroscience research

    2021  Volume 171, Page(s) 9–18

    Abstract: Spatiotemporal patterns of neural activity generate brain functions, such as perception, memory, and behavior. Four-dimensional (4-D: x, y, z, t) analyses of such neural activity will facilitate understanding of brain functions. However, conventional two- ...

    Abstract Spatiotemporal patterns of neural activity generate brain functions, such as perception, memory, and behavior. Four-dimensional (4-D: x, y, z, t) analyses of such neural activity will facilitate understanding of brain functions. However, conventional two-photon microscope systems observe single-plane brain tissue alone at a time with cellular resolution. It faces a trade-off between the spatial resolution in the x-, y-, and z-axes and the temporal resolution by a limited point-by-point scan speed. To overcome this trade-off in 4-D imaging, we developed a holographic two-photon microscope for dual-plane imaging. A spatial light modulator (SLM) provided an additional focal plane at a different depth. Temporal multiplexing of split lasers with an optical chopper allowed fast imaging of two different focal planes. We simultaneously recorded the activities of neurons on layers 2/3 and 5 of the cerebral cortex in awake mice in vivo. The present study demonstrated the proof-of-concept of dual-plane two-photon imaging of neural circuits by using the temporally multiplexed SLM-based microscope. The temporally multiplexed holographic microscope, combined with in vivo labeling with genetically encoded probes, enabled 4-D imaging and analysis of neural activities at cellular resolution and physiological timescales. Large-scale 4-D imaging and analysis will facilitate studies of not only the nervous system but also of various biological systems.
    MeSH term(s) Animals ; Brain/diagnostic imaging ; Cerebral Cortex ; Mice ; Microscopy ; Neurons
    Language English
    Publishing date 2021-02-16
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 605842-5
    ISSN 1872-8111 ; 0168-0102 ; 0921-8696
    ISSN (online) 1872-8111
    ISSN 0168-0102 ; 0921-8696
    DOI 10.1016/j.neures.2021.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effects of gem-dihydroperoxides against mutant copper‑zinc superoxide dismutase-mediated neurotoxicity.

    Ueda, Tomoyuki / Inden, Masatoshi / Asaka, Yuta / Masaki, Yuji / Kurita, Hisaka / Tanaka, Wakako / Yamaguchi, Eiji / Itoh, Akichika / Hozumi, Isao

    Molecular and cellular neurosciences

    2018  Volume 92, Page(s) 177–184

    Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis, and death. Although its neuropathology is well investigated, currently, effective treatments are unavailable. The mechanism of ... ...

    Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis, and death. Although its neuropathology is well investigated, currently, effective treatments are unavailable. The mechanism of ALS involves the aggregation and accumulation of several mutant proteins, including mutant copper‑zinc superoxide dismutase (SOD1), TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma (FUS) proteins. Previous reports have shown that excessive oxidative stress, associated with mitochondrial dysfunction and mutant protein accumulation, contributes to ALS pathology. The present study focuses on the promotion of SOD1 misfolding and aggregation by oxidative stress. Having recently synthesized novel organic gem-dihydroperoxides (DHPs) with high anti-oxidant activity, we now examined whether DHPs reduce the mutant SOD1-induced intracellular aggregates involved in oxidative stress. We found that, among DHPs, 12AC2O significantly inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Moreover, immunofluorescence staining with redox-sensitive dyes showed that 12AC2O reduced the excessive level of intracellular mutant SOD1-induced reactive oxygen species (ROS). Additionally, ESR analysis showed that 12AC2O exerts a direct scavenging effect against the hydroxyl radical (OH) and the superoxide anion (O
    MeSH term(s) Animals ; Cell Line, Tumor ; Free Radical Scavengers/chemistry ; Free Radical Scavengers/pharmacology ; Mice ; Mutation ; Neurons/drug effects ; Neurons/metabolism ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Oxidative Stress ; Peroxides/chemistry ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase-1/metabolism
    Chemical Substances Free Radical Scavengers ; Neuroprotective Agents ; Peroxides ; Sod1 protein, mouse (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1)
    Language English
    Publishing date 2018-09-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1046640-x
    ISSN 1095-9327 ; 1044-7431
    ISSN (online) 1095-9327
    ISSN 1044-7431
    DOI 10.1016/j.mcn.2018.09.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity.

    Ueda, Tomoyuki / Inden, Masatoshi / Shirai, Katsuhiro / Sekine, Shin-Ichiro / Masaki, Yuji / Kurita, Hisaka / Ichihara, Kenji / Inuzuka, Takashi / Hozumi, Isao

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 2882

    Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ... ...

    Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ALS-associated mutant copper-zinc superoxide dismutase (SOD1)-mediated toxicity. Ethanol extract of brazilian green propolis (EBGP) protected N2a cells against mutant SOD1-induced neurotoxicity and reduced aggregated mutant SOD1 by induction of autophagy. Kaempferide and kaempferol, the active ingredients of EBGP, also inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Both kaempferide and kaempferol significantly suppressed mutant SOD1-induced superoxide in mitochondria. Western blot analysis showed that kaempferol potentially induced autophagy via the AMP-activated protein kinase (AMPK) - the mammalian target of rapamycin (mTOR) pathway. These results suggest that EBGP containing the active ingredient against mutant SOD1-mediated toxicity is a promising medicine or health food for prevention and treatment of ALS.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Animals ; Antioxidants/chemistry ; Antioxidants/pharmacology ; Autophagy ; Flavonols/chemistry ; Flavonols/pharmacology ; Kaempferols/pharmacology ; Mice ; Motor Neurons/drug effects ; Motor Neurons/metabolism ; Mutation ; Phosphorylation ; Propolis/chemistry ; Propolis/pharmacology ; Protective Agents/chemistry ; Protective Agents/pharmacology ; Protein Aggregates ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase-1/metabolism
    Chemical Substances Antioxidants ; Flavonols ; Kaempferols ; Protective Agents ; Protein Aggregates ; kaempferol (731P2LE49E) ; Propolis (9009-62-5) ; Superoxide Dismutase-1 (EC 1.15.1.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2017-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-03115-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: CD8+, CD56+ (natural killer-like) T-cell lymphoma involving the small intestine with no evidence of enteropathy: clinicopathology and molecular study of five Japanese patients.

    Akiyama, Takashi / Okino, Takeshi / Konishi, Hiroshi / Wani, Yoji / Notohara, Kenji / Tsukayama, Choutatsu / Tsunoda, Tsukasa / Tasaka, Taizo / Masaki, Yuji / Sugihara, Takashi / Sadahira, Yoshito

    Pathology international

    2008  Volume 58, Issue 10, Page(s) 626–634

    Abstract: The present study reports five CD8+, CD56+ (natural killer (NK)-like) T-cell lymphomas involving the small intestine without evidence of enteropathy, from Japan. Three were intestinal T-cell lymphoma. The site of origin of the other two was not ... ...

    Abstract The present study reports five CD8+, CD56+ (natural killer (NK)-like) T-cell lymphomas involving the small intestine without evidence of enteropathy, from Japan. Three were intestinal T-cell lymphoma. The site of origin of the other two was not definitive. Four of five patients underwent emergency operation because of intestinal perforation. The small intestines of these patients had multiple ulcerative lesions with or without demarcated tumors. Histologically, the lymphoma cells were monomorphic or slightly pleomorphic and displayed epitheliotropism of varying degrees. Lymphoma cells of all patients shared the common phenotype: CD3+, CD4-, CD5-, CD8+, CD56+, CD57-, T-cell intracellular antigen-1+, granzyme B+. In contrast to nasal/nasal type NK-cell lymphomas, they had clonal rearrangement of T-cell receptor(TCR) genes and were negative for EBV-encoded RNA. Immunohistochemistry and genetics suggested that three cases were of alpha beta T-cell origin and two cases were of gamma delta T-cell origin. There was no evidence of enteropathy in any patient. The cases followed a clinically aggressive course with a frequent involvement of lung. According to the classification based on the recent genetic studies of European enteropathy-type intestinal T-cell lymphoma (ETL), the present cases could be classified as type 2 ETL.
    MeSH term(s) Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; CD56 Antigen/immunology ; CD8-Positive T-Lymphocytes/immunology ; Clone Cells ; Combined Modality Therapy ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Gene Deletion ; Gene Rearrangement, T-Lymphocyte/genetics ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Intestinal Neoplasms/immunology ; Intestinal Neoplasms/mortality ; Intestinal Neoplasms/pathology ; Intestinal Neoplasms/therapy ; Intestine, Small/pathology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Lymphoma, T-Cell/immunology ; Lymphoma, T-Cell/mortality ; Lymphoma, T-Cell/pathology ; Lymphoma, T-Cell/therapy ; Male ; Middle Aged ; Neoplasm Staging ; Prednisolone/therapeutic use ; RNA, Viral/analysis ; Survival Rate ; Vincristine/therapeutic use
    Chemical Substances Biomarkers, Tumor ; CD56 Antigen ; Epstein-Barr virus encoded RNA 1 ; RNA, Viral ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisolone (9PHQ9Y1OLM)
    Language English
    Publishing date 2008-10
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1194850-4
    ISSN 1440-1827 ; 1320-5463
    ISSN (online) 1440-1827
    ISSN 1320-5463
    DOI 10.1111/j.1440-1827.2008.02281.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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