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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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Article ; Online: Non-invasive visualization of arterial stagnation in a dissected internal carotid artery.

Mano, Tatsuo / Nakayama, Takahiro / Endo, Hironobu / Bono, Keiko / Imafuku, Ichiro

Journal of the neurological sciences

2020 Volume 412, Page(s) 116760

MeSH term(s)	Carotid Artery, Internal/diagnostic imaging ; Carotid Artery, Internal, Dissection ; Cerebral Angiography ; Humans ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging
Language	English
Publishing date	2020-02-24
Publishing country	Netherlands
Document type	Letter
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.2020.116760
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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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Article: Case report: Saccadic ping-pong gaze in progressive supranuclear palsy with predominant postural instability.

Nunomura, Hikari / Kasahara, Taketoshi / Hatano, Taku / Shimada, Hitoshi / Takado, Yuhei / Endo, Hironobu / Inoshita, Ayako / Inomata, Atsuko / Murofushi, Toshihisa / Misawa, Shihoko / Machida, Yutaka / Imai, Hisamasa

Frontiers in neurology

2023 Volume 14, Page(s) 1100931

Abstract: We report a 63-year-old female patient with progressive supranuclear palsy (PSP). She presented predominant postural instability and "saccadic ping-pong gaze" (SPPG). She had unprovoked falls recurrently within a year from the onset of gait disturbance. ... ...

Abstract	We report a 63-year-old female patient with progressive supranuclear palsy (PSP). She presented predominant postural instability and "saccadic ping-pong gaze" (SPPG). She had unprovoked falls recurrently within a year from the onset of gait disturbance. She tended to fall backward with eye closure but had no freezing of gait on examination. She showed no signs of nuchal dystonia, limb tremor, rigidity, spasticity, or ataxia. The dopaminergic response was negative. On the initial examination, her vertical eye movements were normal, but frequent macro square wave jerks and SPPG were observed. SPPG consisted of short-cycle, horizontal conjugate irregular pendular oscillations of the eye position from the midpoint with superimposed small saccades. SPPG was observed usually in the dark, not in the daylight, and with eye closure by using electrooculogram and infrared charge-coupled device imaging. One and a half years after the first examination, she was diagnosed as probable PSP with vertical supranuclear gaze palsy. SPPG was first described in patients who are unconscious by Johkura in 1998 as a "saccadic" variant of "ping-pong gaze (PPG)." PPG, short-cycle periodic alternating gaze, has been described in comatose patients since 1967. On the other hand, abnormal eye movement, which looks the same as SPPG in coma, has been described in conscious patients with PSP or spinocerebellar degeneration (SCD) in Japanese literature since 1975. However, it has been called "transient alternating saccades (TAS)." Nowadays, we believe it is more appropriate to call this abnormal eye movement "SPPG" instead of TAS. Here, we propose that PSP, a neuro-degenerative disease, should be added as one of the etiologies of SPPG. We discuss the differences between PPG/SPPG in coma and SPPG in PSP and the possible pathophysiological mechanism of SPPG in relation to cerebellar oculomotor dysfunctions.
Language	English
Publishing date	2023-03-01
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1100931
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Article ; Online: Serotonergic Neurotransmission in Limbic Regions May Reflect Therapeutic Response of Depressive Patients: A PET Study With 11C-WAY-100635 and 18F-MPPF.

Kitamura, Soichiro / Kimura, Yasuyuki / Takahata, Keisuke / Moriguchi, Sho / Kubota, Manabu / Shimada, Hitoshi / Endo, Hironobu / Takado, Yuhei / Kawamura, Kazunori / Zhang, Ming-Rong / Suhara, Tetsuya / Higuchi, Makoto

The international journal of neuropsychopharmacology

2023 Volume 26, Issue 7, Page(s) 474–482

Abstract: Background: Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors ...

Abstract	Background: Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors has yet to be clarified. 11C-WAY-100635 and 18F-MPPF are positron emission tomography (PET) radioligands for 5-HT1A receptors. While binding of both ligands reflects 5-HT1A receptor density, 18F-MPPF biding may also be affected by extracellular 5-HT concentrations. This dual-tracer PET study explored the neurochemical substrates underlying antidepressant effects in patients with depression. Methods: Eleven patients with depression, including 9 treated with antidepressants, and 16 age- and sex-matched healthy individuals underwent PET scans with 11C-WAY-100635 and 18F-MPPF. Radioligand binding was determined by calculating the nondisplaceable binding potential (BPND). Results: Patients treated with antidepressants showed significantly lower 18F-MPPF BPND in neocortical regions and raphe nuclei, but not in limbic regions, than controls. No significant group differences in 11C-WAY-100635 BPND were found in any of the regions. Significant correlations of BPND between 11C-WAY-100635 and 18F-MPPF were observed in limbic regions and raphe nuclei of healthy controls, but no such associations were found in antidepressant-treated patients. Moreover, 18F-MPPF BPND in limbic regions was significantly correlated with the severity of depressive symptoms. Conclusions: These results suggest a diversity of antidepressant-induced extracellular 5-HT elevations in the limbic system among depressive patients, which is associated with the individual variability of clinical symptoms following the treatment.
MeSH term(s)	Humans ; Carbon Radioisotopes ; Brain/diagnostic imaging ; Brain/metabolism ; Serotonin/metabolism ; Radiopharmaceuticals/metabolism ; Positron-Emission Tomography/methods ; Antidepressive Agents/therapeutic use ; Antidepressive Agents/metabolism ; Synaptic Transmission ; Receptor, Serotonin, 5-HT1A/metabolism
Chemical Substances	N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (71IH826FEG) ; Carbon-11 ; Carbon Radioisotopes ; Serotonin (333DO1RDJY) ; Radiopharmaceuticals ; Antidepressive Agents ; Receptor, Serotonin, 5-HT1A (112692-38-3)
Language	English
Publishing date	2023-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440129-0
ISSN	1469-5111 ; 1461-1457
ISSN (online)	1469-5111
ISSN	1461-1457
DOI	10.1093/ijnp/pyad026
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Article ; Online: Altered Brain Energy Metabolism Related to Astrocytes in Alzheimer's Disease.

Annals of neurology

2023

Abstract: Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to ...

Abstract	Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered brain energy metabolism. Astrocytes are primarily considered glycolytic cells, suggesting a preference for lactate production. This study aimed to examine alterations in astrocytic activities and their association with brain lactate levels in AD. Methods: The study included 30 AD and 30 cognitively unimpaired participants. For AD participants, amyloid and tau depositions were confirmed by positron emission tomography using [ Results: Myo-inositol and lactate levels were higher in AD patients than in cognitively unimpaired participants (p < 0.05). Myo-inositol levels correlated with lactate levels (r = 0.272, p = 0.047). Myo-inositol and lactate levels were positively associated with the Clinical Dementia Rating sum-of-boxes scores (p < 0.05). Significant correlations were noted between myo-inositol levels and plasma glial fibrillary acidic protein, tau phosphorylated at threonine 181 levels, and amyloid and tau positron emission tomography accumulation in the posterior cingulate cortex (p < 0.05). Interpretation: We found high myo-inositol levels accompanied by increased lactate levels in the posterior cingulate cortex in AD patients, indicating a link between reactive astrocytes and altered brain energy metabolism. Myo-inositol and plasma glial fibrillary acidic protein may reflect similar astrocytic changes as biomarkers of AD. ANN NEUROL 2023.
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26797
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Article ; Online: Association of protein distribution and gene expression revealed by positron emission tomography and postmortem gene expression in the dopaminergic system of the human brain.

Yamamoto, Yasuharu / Takahata, Keisuke / Kubota, Manabu / Takeuchi, Hiroyoshi / Moriguchi, Sho / Sasaki, Takeshi / Seki, Chie / Endo, Hironobu / Matsuoka, Kiwamu / Tagai, Kenji / Kimura, Yasuyuki / Kurose, Shin / Mimura, Masaru / Kawamura, Kazunori / Zhang, Ming-Rong / Higuchi, Makoto

European journal of nuclear medicine and molecular imaging

2023 Volume 50, Issue 13, Page(s) 3928–3936

Abstract: Purpose: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new ... ...

Abstract	Purpose: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters. This discrepancy may be due to differences in regulation after transcription between presynaptic and postsynaptic proteins, which have not been studied in the dopaminergic system. Here, we focused on dopamine D1 and D2/D3 receptors and dopamine transporters and investigated their region-wise relationship between mRNA expression and protein distribution. Methods: We examined the region-wise correlation between regional binding potentials of the target region relative to that of non-displaceable tissue (BP Results: We found significant positive correlations between regional BP Conclusion: We found a region-wise correlation between the mRNA expression levels of dopamine D1 and D2 receptors and their respective protein distributions. However, we found no region-wise correlation between the mRNA expression levels of dopamine transporters and their protein distributions, indicating different regulatory mechanisms for the localization of pre- and postsynaptic proteins. These results provide a broader understanding of the application of the transcriptome atlas to neuroimaging studies of the dopaminergic nervous system.
MeSH term(s)	Humans ; Dopamine/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Positron-Emission Tomography/methods ; Receptors, Dopamine D2/genetics ; Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D3/genetics ; Receptors, Dopamine D3/metabolism ; Dopamine Plasma Membrane Transport Proteins/genetics ; Dopamine Plasma Membrane Transport Proteins/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Gene Expression
Chemical Substances	Dopamine (VTD58H1Z2X) ; FLB 457 (107188-66-9) ; Receptors, Dopamine D2 ; Receptors, Dopamine D3 ; Dopamine Plasma Membrane Transport Proteins ; RNA, Messenger
Language	English
Publishing date	2023-08-15
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/s00259-023-06390-2
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Article ; Online: Investigating neural dysfunction with abnormal protein deposition in Alzheimer's disease through magnetic resonance spectroscopic imaging, plasma biomarkers, and positron emission tomography.

Matsuoka, Kiwamu / Hirata, Kosei / Kokubo, Naomi / Maeda, Takamasa / Tagai, Kenji / Endo, Hironobu / Takahata, Keisuke / Shinotoh, Hitoshi / Ono, Maiko / Seki, Chie / Tatebe, Harutsugu / Kawamura, Kazunori / Zhang, Ming-Rong / Shimada, Hitoshi / Tokuda, Takahiko / Higuchi, Makoto / Takado, Yuhei

NeuroImage. Clinical

2023 Volume 41, Page(s) 103560

Abstract: In Alzheimer's disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the ...

Abstract	In Alzheimer's disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the human brain. To clarify the relationship between neuronal dysfunction and abnormal proteins in AD-affected brains, we conducted magnetic resonance spectroscopic imaging (MRSI) and assessed the neurofilament light chain plasma levels (NfL). We evaluated tau and amyloid-β depositions using standardized uptake value ratios (SUVRs) of florzolotau (18F) for tau and
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; tau Proteins/metabolism ; Creatine/metabolism ; Case-Control Studies ; Magnetic Resonance Imaging ; Amyloid beta-Peptides/metabolism ; Positron-Emission Tomography ; Brain/pathology ; Glutamic Acid/metabolism ; Magnetic Resonance Spectroscopy ; Biomarkers/metabolism ; Receptors, Antigen, T-Cell/metabolism
Chemical Substances	tau Proteins ; Creatine (MU72812GK0) ; Amyloid beta-Peptides ; Glutamic Acid (3KX376GY7L) ; Biomarkers ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-12-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2023.103560
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Article ; Online: Association of Tooth Loss with Alzheimer's Disease Tau Pathologies Assessed by Positron Emission Tomography.

Matsumoto, Hideki / Tagai, Kenji / Endo, Hironobu / Matsuoka, Kiwamu / Takado, Yuhei / Kokubo, Naomi / Shimada, Hitoshi / Goto, Tetsuya / Goto, Tazuko K / Higuchi, Makoto

Journal of Alzheimer's disease : JAD

2022 Volume 96, Issue 3, Page(s) 1253–1265

Abstract: Background: Deterioration of the oral environment is one of the risk factors for dementia. A previous study of an Alzheimer's disease (AD) model mouse suggests that tooth loss induces denervation of the mesencephalic trigeminal nucleus and ... ...

Abstract	Background: Deterioration of the oral environment is one of the risk factors for dementia. A previous study of an Alzheimer's disease (AD) model mouse suggests that tooth loss induces denervation of the mesencephalic trigeminal nucleus and neuroinflammation, possibly leading to accelerated tau dissemination from the nearby locus coeruleus (LC). Objective: To elucidate the relevance of oral conditions and amyloid-β (Aβ) and tau pathologies in human participants. Methods: We examined the number of remaining teeth and the biofilm-gingival interface index in 24 AD-spectrum patients and 19 age-matched healthy controls (HCs). They also underwent positron emission tomography (PET) imaging of Aβ and tau with specific radiotracers, 11C-PiB and 18F-PM-PBB3, respectively. All AD-spectrum patients were Aβ-positive, and all HCs were Aβ-negative. We analyzed the correlation between the oral parameters and radiotracer retention. Results: No differences were found in oral conditions between the AD and HC groups. 11C-PiB retentions did not correlate with the oral indices in either group. In AD-spectrum patients, brain-wide, voxel-based image analysis highlighted several regions, including the LC and associated brainstem substructures, as areas where 18F-PM-PBB3 retentions negatively correlated with the remaining teeth and revealed the correlation of tau deposits in the LC (r = -0.479, p = 0.018) primarily with the hippocampal and neighboring areas. The tau deposition in none of the brain regions was associated with the periodontal status. Conclusions: Our findings with previous preclinical evidence imply that tooth loss may enhance AD tau pathogenesis, promoting tau spreading from LC to the hippocampal formation.
MeSH term(s)	Humans ; Alzheimer Disease/complications ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Amyloid beta-Peptides ; Positron-Emission Tomography/methods ; tau Proteins ; Tooth Loss/complications ; Tooth Loss/diagnostic imaging
Chemical Substances	2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole ; Amyloid beta-Peptides ; tau Proteins ; MAPT protein, human
Language	English
Publishing date	2022-07-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230581
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Article ; Online: Low signal intensity in motor cortex on susceptibility-weighted MR imaging is correlated with clinical signs of amyotrophic lateral sclerosis: a pilot study.

Endo, Hironobu / Sekiguchi, Kenji / Shimada, Hitoshi / Ueda, Takehiro / Kowa, Hisatomo / Kanda, Fumio / Toda, Tatsushi

Journal of neurology

2018 Volume 265, Issue 3, Page(s) 552–561

Abstract: There is no reliable objective indicator for upper motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). To determine the clinical significance and potential utility of magnetic resonance (MR) signals, we investigated the relationship between ... ...

Abstract	There is no reliable objective indicator for upper motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). To determine the clinical significance and potential utility of magnetic resonance (MR) signals, we investigated the relationship between clinical symptoms and susceptibility changes in the motor cortex measured using susceptibility-weighted MR imaging taken by readily available 3-T MRI in clinical practice. Twenty-four ALS patients and 14 control subjects underwent 3-T MR T1-weighted imaging and susceptibility-weighted MR imaging with the principles of echo-shifting with a train of observations (PRESTO) sequence. We analysed relationships between relative susceptibility changes in the motor cortex assessed using voxel-based analysis (VBA) and clinical scores, including upper motor neuron score, ALS functional rating scale revised score, and Medical Research Council sum score on physical examination. Patients with ALS exhibited significantly lower signal intensity in the precentral gyrus on susceptibility-weighted MR imaging compared with controls. Clinical scores were significantly correlated with susceptibility changes. Importantly, the extent of the susceptibility changes in the bilateral precentral gyri was significantly correlated with upper motor neuron scores. The results of our pilot study using VBA indicated that low signal intensity in motor cortex on susceptibility-weighted MR imaging may correspond to clinical symptoms, particularly upper motor neuron dysfunction. Susceptibility-weighted MR imaging may be a useful diagnostic tool as an objective indicator of upper motor neuron dysfunction.
MeSH term(s)	Aged ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; Area Under Curve ; Female ; Follow-Up Studies ; Functional Laterality ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/methods ; Male ; Motor Cortex/diagnostic imaging ; Physical Examination ; Pilot Projects ; ROC Curve ; Severity of Illness Index
Language	English
Publishing date	2018-01-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-017-8728-0
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