Kunimasa Arima

National Center of Neurology and Psychiatry, Кодаиры, Tōkyō, Japan

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Publications (131)600.85 Total impact

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    ABSTRACT: Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by formation of multifocal bone cysts and development of leukoencephalopathy, caused by genetic mutations of either DNAX-activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). Although increasing evidence suggests a defect in microglial TREM2/DAP12 function in NHD, the molecular mechanism underlying leukoencephalopathy with relevance to microglial dysfunction remains unknown. TREM2, by transmitting signals via the immunoreceptor tyrosine-based activation motif (ITAM) of DAP12, stimulates phagocytic activity of microglia, and ITAM signaling is counterbalanced by sialic acid-binding immunoglobulin (Ig)-like lectins (Siglecs)-mediated immunoreceptor tyrosine-based inhibitory motif (ITIM) signaling. To investigate a role of CD33, a member of the Siglecs family acting as a negative regulator of microglia activation, in the pathology of NHD, we studied CD33 expression patterns in five NHD brains and 11 controls by immunohistochemistry. In NHD brains, CD33 was identified exclusively on ramified and amoeboid microglia accumulated in demyelinated white matter lesions but not expressed in astrocytes, oligodendrocytes, or neurons. However, the number of CD33-immunoreactive microglia showed great variability from case to case and from lesion to lesion without significant differences between NHD and control brains. These results do not support the view that CD33-expressing microglia play a central role in the development of leukoencephalopathy in NHD brains.
    No preview · Article · Dec 2015 · Neuropathology
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    ABSTRACT: Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer's disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7-18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243-406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau.
    No preview · Article · Nov 2015 · Acta Neuropathologica
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    ABSTRACT: The purpose of this study was to evaluate the clinical impact of addition of (11) C-PiB PET on routine clinical diagnosis of Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI), and to assess diagnostic agreement between clinical criteria and research criteria of the NIA-AA. The diagnosis in 85 patients was made according to clinical criteria. Imaging examinations, including both MRI and SPECT/CT to identify neuronal injury (NI), and (11) C-PiB PET to identify amyloid were performed, and all subjects were re-categorized according to research criteria. Among 40 patients with probable AD dementia (ProAD), 37 were NI-positive, 29 were (11) C-PiB-positive, and 27 who were both NI- and (11) C-PiB-positive were categorized as having "ProAD dementia with a high level of evidence of the AD pathophysiological process". Among 20 patients with possible AD dementia (PosAD), 17 were NI-positive, and 6 who were both NI- and (11) C-PiB-positive were categorized as having "PosAD with evidence of the AD pathophysiological process". Among 25 patients with MCI, 18 were NI-positive, 13 were (11) C-PiB-positive, and 10 who were both NI- and (11) C-PiB-positive were categorized as having "MCI due to AD-high likelihood". Diagnostic concordance between clinical criteria and research criteria may not be high in this study. (11) C-PiB PET may be of value in making the diagnosis of dementia and MCI in cases with high diagnostic uncertainty. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · Psychiatry and Clinical Neurosciences
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    ABSTRACT: Expanded GGGGCC hexanucleotide repeats located in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene represent the most common genetic abnormality for familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Formation of nuclear RNA foci, accumulation of repeat-associated non-ATG-translated dipeptide-repeat proteins, and haploinsufficiency of C9orf72 are proposed for pathological mechanisms of C9ALS/FTD. However, at present, the physiological function of C9orf72 remains largely unknown. By searching on a bioinformatics database named COXPRESdb composed of the comprehensive gene coexpression data, we studied potential C9orf72 interactors. We identified the ATP/GTP binding protein 1 (AGTPBP1) gene alternatively named NNA1 encoding a cytosolic carboxypeptidase whose mutation is causative of the degeneration of Purkinje cells and motor neurons as the most significant gene coexpressed with C9orf72. We verified coexpression and interaction of AGTPBP1 and C9orf72 in transfected cells by immunoprecipitation and in neurons of the human brain by double-labeling immunohistochemistry. Furthermore, we found a positive correlation between AGTPBP1 and C9orf72 mRNA expression levels in the set of 21 human brains examined. These results suggest that AGTPBP1 serves as a C9orf72 interacting partner that plays a role in the regulation of neuronal function in a coordinated manner within the central nervous system.
    Preview · Article · Jun 2015
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    ABSTRACT: Neurodegeneration in bipolar disorder (BPD) is poorly understood. Therefore, the current study was designed to assess the immunohistochemical changes in neurodegenerative markers in patients with BPD. Eleven consecutive autopsy cases diagnosed with BPD were analyzed. Sections were obtained from archival paraffin blocks of representative areas and stained using conventional methods, as well as immunostained with several antibodies to screen for neurodegenerative diseases. Age- and non-argyrophilic grains (AGs) degeneration matched controls were selected for each case. Clinical information was retrospectively collected from medical charts. All patients were men, and the average age of death was 70 years. Neuropathological diagnoses included dementia with grains (2), argyrophilic grain disease (2), corticobasal degeneration (CBD, 1), Lewy body disease (1), hypoxic encephalopathy (1) and cerebral infarction (1). All cases showed AGs to various degrees. Three patients died in their 50s; one demonstrated dementia with Lewy bodies, while the other two showed abundant AGs in the thalamus and amygdala. Of the three patients who died in their 60s, one showed AGs preferentially in the thalamus and amygdala, while the others demonstrated limbic predominance. The patients who died in/after their 70s demonstrated AGs similar to controls, except for the patient with CBD. Our data provides potentiality that neurodegenerative diseases may be an underlying pathology in certain cases of BPD. © 2015 The Authors. Neuropathology published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Society of Neuropathology.
    No preview · Article · Mar 2015 · Neuropathology
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    ABSTRACT: Recently, a whole-exome sequencing (WES) study showed that a rare variant rs145999145 composed of p.Val232Met located in exon 7 of the phospholipase D3 (PLD3) gene confers a doubled risk for late-onset Alzheimer's disease (AD). Knockdown of PLD3 elevates the levels of extracellular amyloid-beta (Aβ), suggesting that PLD3 acts as a negative regulator of Aβ precursor protein (APP) processing. However, the precise cellular location and distribution of PLD3 in AD brains remain largely unknown. By quantitative RT-PCR (qPCR), western blot, immunohistochemistry, and bioinformatics analysis, we studied PLD3 expression patterns and levels in a series of AD and control brains, including amyotrophic lateral sclerosis, Parkinson's disease, multiple system atrophy, and non-neurological cases. The levels of PLD3 mRNA and protein expression were reduced modestly in AD brains, compared with those in non-AD brains. In all brains, PLD3 was expressed constitutively in cortical neurons, hippocampal pyramidal and granular neurons but not in glial cells. Notably, PLD3 immunoreactivity was accumulated on neuritic plaques in AD brains. We identified the human granulin (GRN) gene encoding progranulin (PRGN) as one of most significant genes coexpressed with PLD3 by bioinformatics database search. PLD3 was actually coexpressed and interacted with PGRN both in cultured cells in vitro and in AD brains in vivo. We identified an intense accumulation of PLD3 on neuritic plaques coexpressed with PGRN in AD brains, suggesting that PLD3 plays a key role in the pathological processes of AD.
    Full-text · Article · Nov 2014 · Alzheimer's Research and Therapy
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    ABSTRACT: The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with (18) F-FDG PET and (99m) Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between (18) F-FDG PET and (99m) Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m) Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between (18) F-FDG PET and (99m) Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on (18) F-FDG PET and (99m) Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of (18) F-FDG PET and (99m) Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.
    No preview · Article · Oct 2014 · International Journal of Geriatric Psychiatry
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    ABSTRACT: The Gallyas method is a silver impregnation technique that is essential in the field of neuropathology because of its high sensitivity for the detection of argentophilic inclusion bodies in the central nervous system. In Japan, the Gallyas method has improved and is widely used as the “modified Gallyas method”. However, this method is not popularly used in general pathology laboratories because of the need for special reagents, several staining processes, and skilled techniques. The objective of the current study was to provide a simplified Gallyas method. We omitted the lanthanum nitrate step from the staining process and verified the adequacy in comparison with the original method as well as immunohistochemistry, using specimens from patients of Alzheimer's disease, argyrophilic grain disease, multiple system atrophy, Pick's disease, and Lewy body disease. The simplified method provided good staining to all the structures in archival tissues, compared with the modified Gallyas method in a significantly shorter staining time. The lanthanum nitrate step can be omitted from the modified Gallyas method, resulting in reduction in the number of reagents required and shortening of the staining time.
    Preview · Article · Sep 2014 · Neuropathology

  • No preview · Conference Paper · Jun 2014
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    ABSTRACT: While research on remission in schizophrenia has gained attention, personality characteristics associated with remission in schizophrenia have been under-studied. A functional valine-to-methionine (Val158Met) polymorphism in the catechol-O-methyltransferase (COMT) gene is shown to modify clinical presentation of schizophrenia despite weak or no association with the disorder itself. Studies also report that this polymorphism can affect personality traits. We aimed to examine personality traits of remitted patients with schizophrenia as compared to symptomatic patients and healthy controls and to investigate whether the COMT Val158Met polymorphism influences their personality. Scores on the Temperament and Character Inventory were compared between 34 remitted outpatients with schizophrenia, age- and sex-matched 72 symptomatic outpatients with schizophrenia, and matched 247 healthy individuals. The effect of COMT Val158Met polymorphism on personality was examined in each group. The analysis of covariance, controlling for confounding variables, revealed that compared to healthy controls, symptomatic patients exhibited a pervasively altered personality profile whereas remitted patients showed alterations in more limited personality dimensions and demonstrated normal levels of novelty-seeking, reward dependence and cooperativeness. The two-way analysis of covariance, with genotype and sex as between-subject factors and confounders as covariates, revealed that Met carriers demonstrated significantly lower reward dependence and cooperativeness than Val homozygotes in symptomatic patients; while no significant genotype effect was found in remitted patients or in healthy individuals. These findings indicate that remitted patients with schizophrenia have a relatively adaptive personality profile compared to symptomatic patients. The COMT Val158Met polymorphism might have a modulating effect on the relationship between personality and remission.
    No preview · Article · May 2014 · Journal of Psychiatric Research
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    ABSTRACT: Background Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Neuropathologically, NHD exhibits profound loss of myelin and accumulation of axonal spheroids, accompanied by intense gliosis accentuated in the white matter of the frontal and temporal lobes. At present, the molecular mechanism responsible for development of leukoencephalopathy in NHD brains remains totally unknown. Methods By immunohistochemistry, we studied the expression of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, in 5 NHD and 12 control brains. Results In all NHD brains, Nogo-A-positive, CNPase-positive oligodendrocytes surviving in the non-demyelinated white matter intensely expressed LC3. They also expressed ubiquitin, ubiquilin-1, and histone deacetylase 6 (HDAC6) but did not express Beclin 1 or sequestosome 1 (p62). Substantial numbers of axonal spheroids were also labeled with LC3 in NHD brains. In contrast, none of oligodendrocytes expressed LC3 in control brains. Furthermore, surviving oligodendrocytes located at the demyelinated lesion edge of multiple sclerosis (MS) did not express LC3, whereas infiltrating Iba1-positive macrophages and microglia intensely expressed LC3 in MS lesions. Conclusions These results propose a novel hypothesis that aberrant regulation of autophagy might induce oligodendrogliopathy causative of leukoencephalopathy in NHD brains.
    Full-text · Article · May 2014 · Orphanet Journal of Rare Diseases
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    ABSTRACT: TMEM106B is a transmembrane glycoprotein of unknown function located within endosome/lysosome compartments expressed ubiquitously in various cell types. Previously, the genome-wide association study (GWAS) identified a significant association of TMEM106B single nucleotide polymorphisms (SNPs) with development of frontotemporal lobar degeneration with ubiquitinated TAR DNA-binding protein-43 (TDP-43)-positive inclusions (FTLD-TDP), particularly in the patients exhibiting the progranulin (PGRN) gene (GRN) mutations. Recent studies indicate that TMEM106B plays a pathological role in various neurodegenerative diseases, including Alzheimer's disease (AD). However, at present, the precise levels of TMEM106B expression in AD brains remain unknown. By quantitative reverse transcription (RT)-PCR (qPCR), western blot and immunohistochemistry, we studied TMEM106B and PGRN expression levels in a series of AD and control brains, including amyotrophic lateral sclerosis, Parkinson's disease, multiple system atrophy and non-neurological cases. In AD brains, TMEM106B mRNA and protein levels were significantly reduced, whereas PGRN mRNA levels were elevated, compared with the levels in non-AD brains. In all brains, TMEM106B was expressed in the majority of cortical neurons, hippocampal neurons, and some populations of oligodendrocytes, reactive astrocytes and microglia with the location in the cytoplasm. In AD brains, surviving neurons expressed intense TMEM106B immunoreactivity, while senile plaques, neurofibrillary tangles and the perivascular neuropil, almost devoid of TMEM106B, intensely expressed PGRN. We found an inverse relationship between TMEM106B (downregulation) and PGRN (upregulation) expression levels in AD brains, suggesting a key role of TMEM106B in the pathological processes of AD.
    Full-text · Article · Mar 2014 · Alzheimer's Research and Therapy
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    ABSTRACT: Objective Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1β (IL-1B) maturation. Mice deficient for NLRP3 inflammasome components are resistant to experimental autoimmune encephalomyelitis (EAE), suggesting a pro-inflammatory role of NLRP3 inflammasome. However, at present, a pathological role of NLRP3 inflammasome in multiple sclerosis (MS) brains remains unknown. Methods We studied the expression of NLRP3 inflammasome components in active demyelinating lesions of MS by immunohistochemistry. ResultsReactive astrocytes and perivascular macrophages expressed all three components of NLRP3 inflammasome – NLRP3, ASC and CASP1 – along with IL-1B in active demyelinating lesions of MS, active necrotic lesions of neuromyelitis optica (NMO) and acute necrotic lesions of cerebral infarction. In contrast, the levels of expression of NLRP3, ASC, CASP1, and IL-1B were greatly reduced in chronic inactive lesions of MS and gliotic lesions of cerebral infarction. Furthermore, the great majority of ramified and amoeboid microglia did not express NLRP3 in active and inactive MS lesions. ConclusionsNLRP3 inflammasome could be activated chiefly in reactive astrocytes and infiltrating macrophages under the condition of active destruction of brain tissues that potentially provides a danger signal.
    Preview · Article · Dec 2013 · Clinical and Experimental Neuroimmunology
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    ABSTRACT: Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia.
    No preview · Article · Nov 2013 · Journal of Psychiatric Research
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    Preview · Article · Jul 2013 · Alzheimer's Research and Therapy
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    ABSTRACT: Recently, neurobiological studies of the cognitive model of depression have become vastly more important, and a growing number of such studies are being reported. However, the relationship between the proportion of positive and negative automatic thought and activity in the prefrontal and temporal cortices has not yet been explored. We examined the relationship between brain activity and the proportion of positive and negative automatic thought in patients with major depressive disorder (MDD), using multi-channel near-infrared spectroscopy (NIRS). We recruited 75 individuals with MDD (36 females; mean age=39.23±12.49). They completed the Hamilton Rating Scale for Depression, Automatic Thoughts Questionnaire-Revised, Japanese version of the National Adult Reading Test, and the State-Trait Anxiety Inventory. Brain activation was measured by 52-channel NIRS. We found that activation in the vicinity of the right superior temporal gyrus is related to a deviation to negative of the proportion of positive and negative thoughts in individuals with MDD. Left dorsolateral prefrontal cortex activity was higher in the group with comparatively frequent positive thought. Our participants were patients taking antidepressant medication, which is known to influence brain activity. Second, the poor spatial resolution of NIRS increases the difficulty of identifying the measurement position. We found that activation of the prefrontal and temporal cortices is related to the proportion of automatic thoughts in the cognitive model of depression.
    Full-text · Article · Jul 2013 · Journal of Affective Disorders
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    ABSTRACT: The voxel-based morphometry (VBM) technique using brain magnetic resonance imaging (MRI) objectively maps gray matter loss on a voxel-by-voxel basis after anatomic standardization. In patients with Alzheimer's disease (AD), reductions of gray matter volume, mainly in the medial temporal structures, have been reported; however, inhomogeneity and geometric distortion of the field intensity hampers the reproducibility of MRI. In the present study, we developed a novel computed tomography (CT)-based VBM method and used this technique to detect volume loss in AD patients as compared with normal controls. The results were compared with MRI-based VBM using the same subjects. Pittsburgh Compound B ((11)C-PIB) positron emission tomography (PET)/CT was performed and two experts in neuro-nuclear medicine judged whether regional amyloid β load was consistent with a diagnosis of AD. Before the injection of (11)C-PIB, high-quality CT scans were obtained using the same PET/CT equipment. MRI was performed within a mean interval of 25.1 ± 8.2 days before the PET/CT scan. Using statistical parametric mapping 8 (SPM8), the extracted gray matter images from CT and MRI were spatially normalized using a gray matter template and smoothed using a Gaussian kernel. Group comparisons were performed using SPM8 between five (11)C-PIB-positive patients with probable AD and seven (11)C-PIB-negative age-matched controls with normal cognition. Gray matter volumes in the bilateral medial temporal areas were reduced in the AD group as compared with the cognitively normal group in both CT-based VBM (in the left; P < 0.0001, cluster size 2776 and in the right; P < 0.0001, cluster size 630) and MRI-based VBM (in the left; P < 0.0001, cluster size 381 and in the right, P < 0.0001, cluster size 421). This newly developed CT-based VBM technique can detect significant atrophy in the entorhinal cortex in probable AD patients as previously reported using MRI-based VBM. However, CT-VBM was more sensitive and revealed larger areas of significant atrophy than MR-VBM.
    Full-text · Article · Jul 2013 · Brain and Behavior
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    ABSTRACT: Objectives Kir4.1, an inwardly rectifying potassium channel expressed on perivascular and perisynaptic end-feet of astrocytes, plays a pivotal role in the spatial buffering of the potassium in the brain. A recent study showed that autoantibodies directed to Kir4.1 are detectable in the serum derived from approximately half of the patients with multiple sclerosis (MS) and clinically isolated syndrome, although their pathogenic roles should be elucidated. Methods We studied Kir4.1 expression in MS and control brains by immunohistochemistry. ResultsWe found that reactive astrocytes expressed an intense immunoreactivity for Kir4.1 in active demyelinating lesions of MS, active lesion edges of neuromyelitis optica, ischemic lesion edges of cerebral infarction and neurodegenerative lesions of Alzheimer's disease. Reactive astrocytes accumulated in active MS lesions coexpressed Kir4.1 and AQP4. A subset of amyloid plaques in Alzheimer's disease brains also expressed Kir4.1. In contrast, infiltrating macrophages, activated microglia and surviving oligodendrocytes in active MS lesions did not express Kir4.1. Furthermore, cultured human astrocytes expressed Kir4.1, and the expression levels were not altered by exposure to tumor necrosis factor-α or interleukin-1β, but were elevated by transforming growth factor-β1. Conclusions These results show that reactive astrocytes abundantly express Kir4.1, and Kir4.1 immunoreactivity is not lost in active demyelinating lesions of MS.
    Full-text · Article · Jun 2013 · Clinical and Experimental Neuroimmunology
  • J Satoh · H Tabunoki · T Ishida · Y Saito · K Arima
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    ABSTRACT: Aims: Ubiquilin-1 acts as an adaptor protein that mediates the translocation of polyubiquitinated proteins to the proteasome for degradation. Although previous studies suggested a key role of ubiquilin-1 in the pathogenesis of Alzheimer's disease (AD), a direct relationship between ubiquilin-1 and Hirano bodies in AD brains remains unknown. Methods: By immunohistochemistry, we studied ubiquilin-1 and ubiquilin-2 expression in the frontal cortex and the hippocampus of six AD and 13 control cases. Results: Numerous Hirano bodies, accumulated in the hippocampal CA1 region of AD brains, expressed intense immunoreactivity for ubiquilin-1. They were much less frequently found in control brains. However, Hirano bodies did not express a panel of markers for proteasome, autophagosome or pathogenic proteins, such as ubiquilin-2, ubiquitin, p62, LC3, beclin-1, HDAC6, paired helical filament (PHF)-tau, protein-disulphide isomerase (PDI) and phosphorylated TDP-43, but some of them expressed C9orf72. Ubiquilin-1-immunoreactive deposits were classified into four distinct morphologies, such as rod-shaped structures characteristic of Hirano bodies, dystrophic neurites contacting senile plaques, fragmented structures accumulated in the lesions affected with severe neuronal loss, and thread-shaped structures located mainly in the molecular layer of the hippocampus. Conclusions: Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in AD brains, suggesting that aberrant expression of ubiquilin-1 serves as one of pathological hallmarks of AD.
    No preview · Article · Feb 2013 · Neuropathology and Applied Neurobiology
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    ABSTRACT: Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded.
    No preview · Article · Jan 2013 · Journal of Psychiatric Research

Publication Stats

4k Citations
600.85 Total Impact Points

Institutions

  • 1989-2015
    • National Center of Neurology and Psychiatry
      • • Department of Mental Disorder Research
      • • Department of Neurology
      • • Department of Immunology
      Кодаиры, Tōkyō, Japan
  • 2012
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 1991-2004
    • The University of Tokyo
      Tōkyō, Japan
  • 2003
    • Tokyo Metropolitan Institute
      Edo, Tōkyō, Japan
  • 2002
    • Tokyo Medical and Dental University
      • Department of Neuropathology
      Edo, Tōkyō, Japan
  • 1998
    • Jichi Medical University
      • Department of Pediatrics
      Tochigi, Tochigi-ken, Japan