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Ryo Yamasaki Last modified date:2018.06.25

Associate Professor / Neurology
Neurological Institute
Faculty of Medical Sciences


Graduate School
Undergraduate School
Other Organization
Administration Post
Other
Other
Other
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Other


E-Mail
Homepage
http://www.med.kyushu-u.ac.jp/neuro/
http://www.med.kyushu-u.ac.jp/neuro/
Phone
092-642-5340
Fax
092-642-5352
Academic Degree
M.D, Ph.D
Country of degree conferring institution (Overseas)
No
Field of Specialization
Neuroscience
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
We investigate the model mice of amyotrophic lateral sclerosis, from the view point of the neuroprotective function of non-neuronal cells like microglia, astrocytes, etc. We found the impaired activation ability of microglia harvested from ALS model mice. It indicates the impaired neuroprotective function of ALS model mice microglia.
And also we are now starting the investigation of the white blood cell from the ALS patients.
Research
Research Interests
  • Functional analysis of auto-antibody against neurofascin 155 in CIDP patients.
    keyword : CIDP
    2012.07.
  • Functional analysis of Connexins in multiple sclerosis model mice (EAE)
    keyword : Multiple sclerosis, experimental autoimmune encephalomyelitis, connexin
    2014.04.
  • Early strong intrathecal inflammation in cerebellar type multiple system atrophy by cerebrospinal fluid cytokine/chemokine profiles: a case control study
    keyword : Multiple system atrophy, Cerebrospinal fluid, Cytokine, Interleukin-6, Monocyte chemoattractant protein-1, Magnetic resonance imaging
    2014.04.
  • Elucidation of the mechanisms of neural damage in chronic stage multiple sclerosis model mice with glial inflammation
    keyword : Multiple Sclerosis, microglia, astroglia, connexins
    2012.04~2016.03.
  • Elucidation of the mechanisms of the accumulation of mutant SOD1 peptide in ALS model mice.
    keyword : ALS, mutant SOD1, microglia
    2012.04~2015.03.
  • Development of brand-new treatment for the atopy-related allodynia in atopic diathesis model mice.
    keyword : Bronchial asthma, microglia, astroglia, glial inflammation, allodynia
    2015.04~2016.03.
  • Induction and analysis of the atopic myelitis model mice.
    Atopic myelitis reone of the eosinophilic myelitis which are seen in atopic disease patients, and the number is increasing. They feel leg weakness. dysesthesia and general fatigue. We have established new diagnostic criteria (2012), and the number of patients are increasing.We are going to make mice model for bronchial asthma, atopic dermatitis and so on, to check the glial inflammation in central nervous system.
    keyword : Microglia, atopic deaematitis
    2012.10~2014.12.
  • Elucidating the roles of immune cells in the inflammatory lesions of central nervous system
    keyword : microglia, multiple sclerosis, demyelinating disorders, glial inflammations, cytokine
    2012.04~2013.03.
  • I conduct clinical neurology and a neurosciences study.
    The mechanism of amyotrophic lateral sclerosis (ALS) still remain unknown, and the therapy is limited, too. The elucidation of the mechanism of ALS is the mission of the university, and the immediate therapy development is urgent business.
    The spinal cord of the ALS reveals the colonization of monocytes-based cells, activation with a denaturing dropout of the motor nerve, but the role of these cells is not apparent. It is very likely that it contributes to clinical condition elucidation to analyze the function of these cells in detail.
    We are analyzing the effect that a mechanism of the motor nerve degeneration and a non-neuronal cell give to these using an ALS model mouse.
    keyword : Amyotrophic lateral sclerosis, microglia, SOD1
    2008.01~2009.12.
Academic Activities
Reports
1. Autoantibody in chronic inflammatory neuropathies.
Papers
1. Ryo Yamasaki, Early strong intrathecal inflammation in cerebellar type multiple system atrophy by cerebrospinal fluid cytokine/chemokine profiles: a case control study., J Neuroinflammation, 2017.04, Background: The pathology of multiple system atrophy cerebellar-type (MSA-C) includes glial inflammation; however cerebrospinal fluid (CSF) inflammatory cytokine profiles have not been investigated. In this study, we determined CSF cytokine/chemokine/growth factor profiles in MSA-C and compared them with those in hereditary spinocerebellar ataxia (SCA). Methods: We collected clinical data and CSF from 20 MSA-C patients, 12 hereditary SCA patients, and 15 patients with other non-inflammatory neurological diseases (OND), and measured 27 cytokines/chemokines/growth factors using a multiplexed fluorescent bead-based immunoassay. The size of each part of the hindbrain and hot cross bun sign (HCBS) in the pons were studied by magnetic resonance imaging.Results: Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-7, IL-12, and IL-13 levels were significantly higher in MSA-C and SCA compared with OND. In MSA-C, IL-5, IL-6, IL-9, IL-12, IL-13, platelet-derived growth factor-bb, macrophage inflammatory protein (MIP)-1α, and GM-CSF levels positively correlated with anteroposterior diameters of the pontine base, vermis, or medulla oblongata. By contrast, in SCA patients, IL-12 and MIP-1α showed significant negative correlations with anteroposterior diameters of the pontine base, and unlike MSA-C, there was no cytokine with a positive correlation in SCA. IL-6 was significantly higher in MSA-C patients with the lowest grade of HCBS compared with those with the highest grade. Macrophage chemoattractant protein-1 (MCP-1) had a significant negative correlation with disease duration only in MSA-C patients. Tumor necrosis factor-alpha, IL-2, IL-15, IL-4, IL-5, IL-10, and IL-8 were all significantly lower in MSA-C and SCA compared with OND, while IL-1ra, an anti-inflammatory cytokine, was elevated only in MSA-C. IL-1β and IL-8 had positive correlations with Unified Multiple System Atrophy Rating Scale part 1 and 2, respectively, in MSA-C.Conclusions: Although CSF cytokine/chemokine/growth factor profiles were similar between MSA-C and SCA, pro-inflammatory cytokines, such as IL-6, GM-CSF, and MCP-1, correlated with the disease stage in a way higher at the beginning only in MSA-C, reflecting early stronger intrathecal inflammation..
2. Ryo Yamasaki, Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation., J Neurosci, 2016.11, Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia. Microarray analysis of isolated microglia revealed a dysregulated phenotype showing upregulation of M1 macrophage markers and downregulation of M2 markers in atopic mice. Among the cell surface protein genes, endothelin receptor type B (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB expression was en- hanced in microglia and astroglia, whereas endothelin-1, an EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No EDNRA expression was found in the spinal cord. Expression of FBJ murine osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished glial and neural activation and allodynia. We found increased serum endothelin-1 in atopic patients with myelitis and neuropathic pain, and activation of spinal microglia and astroglia with EDNRB upregulation in an autopsied case. These results suggest that allergic inflammation induces diffuse glial activation, influencing the nociceptive system via the EDNRB pathway..
3. Ryo Yamasaki, Richard Ransohoff, Differential roles of microglia and monocytes in the inflamed central nervous system., J Exp Med, 2014.07.
4. Ryo Yamasaki, Nobutoshi Kawamura, Takuya Matsushita, Matsuse Dai, Hiroyuki Murai, Jun-ichi Kira, Anti-neurofascin antibody in patients with combined central and peripheral demyelination., Neurology, 2013.08, We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD).
METHODS:
We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells.
RESULTS:
At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody-positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms.
CONCLUSION:
Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange..
5. Ryo Yamasaki, Tanaka M, Fukunaga M, Tateishi T, Kikuchi H, Motomura K, Matsushita T, Ohyagi Y, Kira J, Restoration of microglial function by granulocyte-colony stimulating factor in ALS model mice., J Neuroimmunol. , 2010.12.
6. Ryo Yamasaki, Jian Zhang, Ichiro Koshiishi, Dewi F. Sastradipura Suniarti, Zhou Wu, Christoph Peters, Michael Schwake, Yasuo Uchiyama, Jun-ichi Kira, Paul Saftig, Hideo Utsumi, Hiroshi Nakanishi , Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in the cathepsin D-deficient mice. , Molecular and Cellular Neuroscience , 2007.08.
Works, Software and Database
1. .
Presentations
1. 山﨑 亮, 松下 拓也, 村井 弘之, 吉良 潤一, 河村 信利, Anti-neurofascin antibody in patients with combined central and peripheral demyelination, ECTRIMS, 2013.10, Background: Growing reports indicated that some multiple sclerosis (MS) patients have peripheral demyelinations and also some of the chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients have demyelinating lesions in the central nervous system (CNS). These combined central and peripheral demyelinations (CCPD) patients have unique characteristics in clinical signs, medical examinations and responses in treatment, but it is still controversial if these patients are distinct from MS or CIDP.
Objectives: We aimed to identify the target antigens for CCPD and to characterize clinical course of CCPD patients.
Methods: We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and CIDP cases. We then measured the level of antibody to the relevant antigen in 7 CCPD patients, 16 CIDP patients, 20 MS patients, 20 patients with Guillain-Barré syndrome (GBS), 21 patients with other neuropathies (ON), and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells. We have also reviewed the clinical data of CCPD patients.
Results: At the initial screening, sera from two CCPD patients showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect co-localization with pan-neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in CCPD patients, 10% in MS patients, 25% in CIDP patients, 15% in GBS patients, and 0% in ON patients and HC. The cell-based assay detected serum anti-neurofascin antibody in 5/7 CCPD patients; all others were negative. CSF samples from three CCPD patients examined were all positive. In anti-neurofascin antibody-positive CCPD patients, including those with a limited response to corticosteroids, intravenous immunoglobulin or plasma exchange alleviated the symptoms.
Conclusion: Anti-neurofascin antibody is frequently present in CCPD patients. Recognition of this antibody may be important, because antibody-positive CCPD patients respond well to intravenous immunoglobulin or plasma exchange.
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2. The impaired neuroprotective function of microglia in the mutant superoxide dismutase 1 transgenic mice.
Membership in Academic Society
  • Society for Neuroscience
Educational
Educational Activities
Our major fields are the Clinical neurology, and Neurosciences.