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  1. Article ; Online: Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury.

    Miyata, Mari / Takahata, Keisuke / Sano, Yasunori / Yamamoto, Yasuharu / Kurose, Shin / Kubota, Manabu / Endo, Hironobu / Matsuoka, Kiwamu / Tagai, Kenji / Oya, Masaki / Hirata, Kosei / Saito, Fumie / Mimura, Masaru / Kamagata, Koji / Aoki, Shigeki / Higuchi, Makoto

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 7129

    Abstract: Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and ... ...

    Abstract Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV-adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK-SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann-Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10
    MeSH term(s) Humans ; Brain Concussion ; Mammillary Bodies ; Brain ; Memory Disorders/etiology ; Athletes/psychology ; Brain Injuries, Traumatic/complications
    Language English
    Publishing date 2024-03-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-57383-6
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  2. Article ; Online: In vivo

    Kubota, Manabu / Endo, Hironobu / Takahata, Keisuke / Tagai, Kenji / Suzuki, Hisaomi / Onaya, Mitsumoto / Sano, Yasunori / Yamamoto, Yasuharu / Kurose, Shin / Matsuoka, Kiwamu / Seki, Chie / Shinotoh, Hitoshi / Kawamura, Kazunori / Zhang, Ming-Rong / Takado, Yuhei / Shimada, Hitoshi / Higuchi, Makoto

    Brain communications

    2024  Volume 6, Issue 2, Page(s) fcae075

    Abstract: Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. ...

    Abstract Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features.
    Language English
    Publishing date 2024-03-01
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcae075
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  3. Article ; Online: Findings of

    Bun, Shogyoku / Moriguchi, Sho / Tezuka, Toshiki / Sato, Yoshiaki / Takahata, Keisuke / Seki, Morinobu / Nakajima, Shinichiro / Yamamoto, Yasuharu / Sano, Yasunori / Suzuki, Natsumi / Morimoto, Ayaka / Ueda, Ryo / Tabuchi, Hajime / Ito, Daisuke / Mimura, Masaru

    Neuropsychopharmacology reports

    2022  

    Abstract: Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive ... ...

    Abstract Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions.
    Aims: 18
    Methods: In the present pilot study, we performed
    Results: The uptake of
    Discussion & conclusion: Our results add to accumulating evidence suggesting that
    Language English
    Publishing date 2022-07-17
    Publishing country United States
    Document type Journal Article
    ISSN 2574-173X
    ISSN (online) 2574-173X
    DOI 10.1002/npr2.12281
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  4. Article ; Online: First-in-human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with

    Takahata, Keisuke / Seki, Chie / Kimura, Yasuyuki / Kubota, Manabu / Ichise, Masanori / Sano, Yasunori / Yamamoto, Yasuharu / Tagai, Kenji / Shimada, Hitoshi / Kitamura, Soichiro / Matsuoka, Kiwamu / Endo, Hironobu / Shinotoh, Hitoshi / Kawamura, Kazunori / Zhang, Ming-Rong / Takado, Yuhei / Higuchi, Makoto

    European journal of nuclear medicine and molecular imaging

    2022  Volume 49, Issue 9, Page(s) 3150–3161

    Abstract: Purpose: Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-inflammatory arachidonic acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and anti-inflammatory agents. ...

    Abstract Purpose: Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-inflammatory arachidonic acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and anti-inflammatory agents. Although MAGL dysfunction has been implicated in neuropsychiatric disorders, it has never been visualized in vivo in human brain. The primary objective of the current study was to visualize MAGL in the human brain using the novel PET ligand
    Methods: Seven healthy males underwent 120-min dynamic
    Results: 18
    Conclusions: Here, we provide the first demonstration of in vivo visualization of MAGL in the human brain.
    MeSH term(s) Brain/diagnostic imaging ; Brain/metabolism ; Cannabinoids/metabolism ; Humans ; Male ; Monoacylglycerol Lipases/metabolism ; Positron-Emission Tomography/methods ; Reproducibility of Results ; Tissue Distribution
    Chemical Substances Cannabinoids ; Monoacylglycerol Lipases (EC 3.1.1.23)
    Language English
    Publishing date 2022-01-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-021-05671-y
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  5. Article ; Online: Correction to: First‑in‑human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with

    Takahata, Keisuke / Seki, Chie / Kimura, Yasuyuki / Kubota, Manabu / Ichise, Masanori / Sano, Yasunori / Yamamoto, Yasuharu / Tagai, Kenji / Shimada, Hitoshi / Kitamura, Soichiro / Matsuoka, Kiwamu / Endo, Hironobu / Shinotoh, Hitoshi / Kawamura, Kazunori / Zhang, Ming-Rong / Takado, Yuhei / Higuchi, Makoto

    European journal of nuclear medicine and molecular imaging

    2022  Volume 49, Issue 9, Page(s) 3299

    Language English
    Publishing date 2022-04-09
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-022-05795-9
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  6. Article ; Online: Positron Emission Tomography Assessments of Phosphodiesterase 10A in Patients With Schizophrenia.

    Kubota, Manabu / Takahata, Keisuke / Matsuoka, Kiwamu / Sano, Yasunori / Yamamoto, Yasuharu / Tagai, Kenji / Tarumi, Ryosuke / Suzuki, Hisaomi / Kurose, Shin / Nakajima, Shinichiro / Shiwaku, Hiroki / Seki, Chie / Kawamura, Kazunori / Zhang, Ming-Rong / Takahashi, Hidehiko / Takado, Yuhei / Higuchi, Makoto

    Schizophrenia bulletin

    2022  Volume 49, Issue 3, Page(s) 688–696

    Abstract: Background and hypothesis: Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been ... ...

    Abstract Background and hypothesis: Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels.
    Study design: This study included 27 patients with schizophrenia, with 5 antipsychotic-free cases, and 27 healthy controls. Positron emission tomography with [18F]MNI-659, a specific PDE10A radioligand, was employed to quantify PDE10A availability by measuring non-displaceable binding potential (BPND) of the ligand in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. BPND estimates were compared between patients and controls while controlling for age and gender. BPND correlations were examined with behavioral and clinical measures, along with regional glutamate levels quantified by the magnetic resonance spectroscopy.
    Study results: Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on BPND (p = .03). A posthoc test showed a trend-level higher sensorimotor striatal BPND in patients, although it did not survive multiple comparison corrections. BPND in controls in this subregion was significantly and negatively correlated with the Tower of London scores, a cognitive subtest. Striatal or dorsolateral prefrontal glutamate levels did not correlate significantly with BPND in either group.
    Conclusions: The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia.
    MeSH term(s) Humans ; Schizophrenia/diagnostic imaging ; Phosphoric Diester Hydrolases/metabolism ; Positron-Emission Tomography/methods ; Basal Ganglia ; Glutamates
    Chemical Substances Phosphoric Diester Hydrolases (EC 3.1.4.-) ; Glutamates ; PDE10A protein, human (EC 3.1.4.-)
    Language English
    Publishing date 2022-12-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbac181
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  7. Article ; Online: An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with

    Tagai, Kenji / Ikoma, Yoko / Endo, Hironobu / Debnath, Oiendrila Bhowmik / Seki, Chie / Matsuoka, Kiwamu / Matsumoto, Hideki / Oya, Masaki / Hirata, Kosei / Shinotoh, Hitoshi / Takahata, Keisuke / Kurose, Shin / Sano, Yasunori / Ono, Maiko / Shimada, Hitoshi / Kawamura, Kazunori / Zhang, Ming-Rong / Takado, Yuhei / Higuchi, Makoto

    NeuroImage

    2022  Volume 264, Page(s) 119763

    Abstract: Positron emission tomography (PET) ... ...

    Abstract Positron emission tomography (PET) with
    Language English
    Publishing date 2022-11-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2022.119763
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  8. Article ; Online: Two pathways differentially linking tau depositions, oxidative stress, and neuronal loss to apathetic phenotypes in progressive supranuclear palsy.

    Matsuoka, Kiwamu / Takado, Yuhei / Tagai, Kenji / Kubota, Manabu / Sano, Yasunori / Takahata, Keisuke / Ono, Maiko / Seki, Chie / Matsumoto, Hideki / Endo, Hironobu / Shinotoh, Hitoshi / Sahara, Yasuka / Obata, Takayuki / Near, Jamie / Kawamura, Kazunori / Zhang, Ming-Rong / Suhara, Tetsuya / Shimada, Hitoshi / Higuchi, Makoto

    Journal of the neurological sciences

    2022  Volume 444, Page(s) 120514

    Abstract: Patients with progressive supranuclear palsy (PSP) frequently exhibit apathy but the neuropathological processes leading to this phenotype remain elusive. We aimed to examine the involvement of tau protein depositions, oxidative stress (OS), and neuronal ...

    Abstract Patients with progressive supranuclear palsy (PSP) frequently exhibit apathy but the neuropathological processes leading to this phenotype remain elusive. We aimed to examine the involvement of tau protein depositions, oxidative stress (OS), and neuronal loss in the apathetic manifestation of PSP. Twenty patients with PSP and twenty-three healthy controls were enrolled. Tau depositions and brain volumes were evaluated via positron-emission tomography (PET) using a specific probe,
    MeSH term(s) Humans ; tau Proteins/metabolism ; Supranuclear Palsy, Progressive/diagnostic imaging ; Supranuclear Palsy, Progressive/complications ; Apathy ; Brain/pathology ; Positron-Emission Tomography/methods ; Oxidative Stress
    Chemical Substances tau Proteins
    Language English
    Publishing date 2022-12-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80160-4
    ISSN 1878-5883 ; 0022-510X ; 0374-8642
    ISSN (online) 1878-5883
    ISSN 0022-510X ; 0374-8642
    DOI 10.1016/j.jns.2022.120514
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  9. Article ; Online: Differential associations of dopamine synthesis capacity with the dopamine transporter and D2 receptor availability as assessed by PET in the living human brain.

    Yamamoto, Yasuharu / Takahata, Keisuke / Kubota, Manabu / Takano, Harumasa / Takeuchi, Hiroyoshi / Kimura, Yasuyuki / Sano, Yasunori / Kurose, Shin / Ito, Hiroshi / Mimura, Masaru / Higuchi, Makoto

    NeuroImage

    2020  Volume 226, Page(s) 117543

    Abstract: Background: The dopamine (DA) neurotransmission has been implicated in fundamental brain functions, exemplified by movement controls, reward-seeking, motivation, and cognition. Although dysregulation of DA neurotransmission in the striatum is known to ... ...

    Abstract Background: The dopamine (DA) neurotransmission has been implicated in fundamental brain functions, exemplified by movement controls, reward-seeking, motivation, and cognition. Although dysregulation of DA neurotransmission in the striatum is known to be involved in diverse neuropsychiatric disorders, it is yet to be clarified whether components of the DA transmission, such as synthesis, receptors, and reuptake are coupled with each other to homeostatically maintain the DA neurotransmission. The purpose of this study was to investigate associations of the DA synthesis capacity with the availabilities of DA transporters and D2 receptors in the striatum of healthy subjects.
    Methods: First, we examined correlations between the DA synthesis capacity and DA transporter availability in the caudate and putamen using PET data with L-[β-
    Results: We found a significant positive correlation between the DA synthesis capacity and DA transporter availability in the putamen, while no significant correlations between the DA synthesis capacity and D2 receptor availability in the striatum.
    Conclusion: The intimate association of the DA synthesis rate with the presynaptic reuptake of DA indicates homeostatic maintenance of the baseline synaptic DA concentration. In contrast, the total abundance of D2 receptors, which consist of presynaptic autoreceptors and postsynaptic modulatory receptors, may not have an immediate relationship to this regulatory mechanism.
    MeSH term(s) Adult ; Brain/diagnostic imaging ; Brain/metabolism ; Caudate Nucleus/diagnostic imaging ; Caudate Nucleus/metabolism ; Dopamine/biosynthesis ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Humans ; Male ; Positron-Emission Tomography ; Putamen/diagnostic imaging ; Putamen/metabolism ; Receptors, Dopamine D2/metabolism ; Synaptic Transmission/physiology ; Young Adult
    Chemical Substances Dopamine Plasma Membrane Transport Proteins ; Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2020-11-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2020.117543
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  10. Article ; Online: A first-in-human study of

    Kubota, Manabu / Seki, Chie / Kimura, Yasuyuki / Takahata, Keisuke / Shimada, Hitoshi / Takado, Yuhei / Matsuoka, Kiwamu / Tagai, Kenji / Sano, Yasunori / Yamamoto, Yasuharu / Okada, Maki / Kikuchi, Tatsuya / Ichise, Masanori / Kawamura, Kazunori / Zhang, Ming-Rong / Higuchi, Makoto

    European journal of nuclear medicine and molecular imaging

    2021  Volume 48, Issue 9, Page(s) 2846–2855

    Abstract: Purpose: Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been ... ...

    Abstract Purpose: Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand
    Methods: Seven healthy males underwent a 90-min PET scan after injection of
    Results: PET images with
    Conclusion: We have provided the first demonstration of PET visualization of PDE7 in human brains.
    MeSH term(s) Algorithms ; Brain/diagnostic imaging ; Cyclic Nucleotide Phosphodiesterases, Type 7 ; Humans ; Ligands ; Male ; Positron-Emission Tomography ; Radiopharmaceuticals
    Chemical Substances Ligands ; Radiopharmaceuticals ; Cyclic Nucleotide Phosphodiesterases, Type 7 (EC 3.1.4.17)
    Language English
    Publishing date 2021-02-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-021-05235-0
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