|Ryo Yamasaki||Last modified date：2018.06.25|
Associate Professor / Neurology / Neurological Institute / Faculty of Medical Sciences
|Ryo Yamasaki||Last modified date：2018.06.25|
|1.||Ryo Yamasaki, Mei Fang, Yinan Zhao, Hayato Une, Hiroo Yamaguchi, Jun-ichi Kira, Astroglial and oligodendroglial connexins differentially modulate acute and chronic experimental autoimmune encephalomyelitis, The 22nd Annual Meeting of the Japan Glia, 2017.12.|
|2.||Ryo Yamasaki MD, PhD, Yinan Zhao, MD, Hiroo Yamaguchi MD, PhD, Jun-ichi Kira MD, PhD., Oligodendroglia-specific Connexin 47 deletion induced relapse-remitting EAE model mice, 10th PACTRIMS Ho Chi Minh City, Vietｎam, 2017.11.|
|3.||Ryo Yamasaki, Hiroo Yamaguchi, Takuya Matsushita, Takayuki Fujii, Akio Hiwatashi, Jun-ichi Kira, Early strong intrathecal inflammation in cerebellar type multiple system atrophy (MSA-C) based on cerebrospinal fluid cytokine and chemokine profiles, XXIII World Congress of Neurology（WCN2017）, 2017.09.|
|4.||山﨑 亮, Astroglial (Cx30, Cx43) and oligodendroglial (Cx47) connexins modulate acute and chronic experimental autoimmune encephalomyelitis (EAE)
, 第4回 MSサマーカレッジ, 2017.08.
|5.||山﨑 亮, Allergic inflammation affects to CNS innate immunity and glial inflammation., Basic Research Forum, 2016.12.|
|6.||山﨑 亮, Mei Fang, Hiroo Yamaguchi, Jun-ichi Kira, Functional analysis of Cx30 in experimental autoimmune encephalomyelitis, 141st Annual meeting of the american neurological association, 2016.10, Objective: Connexins are known to compose gap junctions by a pair of hemichannels connected in a head to head configuration. Each hemichannel is composed by hexameric cluster of connexins. There are 20 members of connexins known as connexin family in mice, and are expressed on each cell surface in different fashion. Connexin 30 (Cx30) is mainly expressed on the surface of oligodendroglia and astrocyte in central nervous system (CNS), but little is known about the functional relevance in neuroinflammatory diseases. To elucidate the role of Cx30 in the pathogenesis of neuroinflammatory disease, we induced experimental autoimmune encephalomyelitis (EAE) on Cx30 knock-out (Cx30-KO) mice and analyzed the clinical and neuropathological findings with wild-type control.
Methods: C57BL/6J and Cx30-KO mice > 12 weeks of age were used in this study (N > 3 in each group). EAE was induced by immunization of mice with MOG35-55 peptide emulsified in CFA at a dose of 200 μg per mouse, followed by the administration of pertussis toxin (500 ng per mouse) on days 0 and 2. Mice were sacrificed and brain, spinal cord, spleen, and optic nerve were harvested for immunohistochemical analyses at the acute and chronic phases of EAE. Mice with EAE were scored as follows: 0, no disease; 1, limp tail; 2, abnormal gait and hind limb weakness (shaking); 2.5, paralysis of one hind limb; 3, paralysis of two hind limb; 3.5, ascending paralysis (able to move around); 4, tetraplegia; and 5, moribund (death). At the onset and chronic stage of EAE, mononuclear cells were isolated and analyzed by flow cytometry to check the distinct characteristics of cellular populations in inflamed CNS lesions.
Results: Initial screening of immunohistological difference revealed basic activation of microglial cells in naïve Cx30-KO mice without any behavioral phenotype. Clinical signs of EAE were ameliorated in the Cx30-KO mice than in the control group mainly during the chronic phase of disease course. Immunohistochemical analyses of the fourth lumbar segment, brain and optic nerve revealed increased number of microglia in the Cx30-KO mice. Flow cytometric analysis also confirmed the findings. In contrast, there were no significant change in astroglial or oligodendroglial phenotype.
Conclusion: Microglial activation appears to be the key factor in the Cx30-KO mice EAE with alleviation of chronic disease scores. Unexpectedly, microglia were already activated in naïve CNS, indicating protective phenotypic change of microglia in Cx30-KO mice..
|7.||山﨑 亮, 方 梅, 藤井 敬之, 李 広瑞, 吉良 潤一, Atopic model mice express more severe signs at the chronic phase of EAE, 第57回日本神経学会学術大会, 2016.05.|
|8.||山﨑 亮, Wang Bing, Fang Mei, 藤井 敬之, 城戸 瑞穂, 吉良 潤一, A mouse model of atopic diathesis displaying tactile allodynia with glial inflammation in the spinal cord, XII European Meeting on Glial Cells in Health and Disease Bilbao, 2015.06.|
|9.||山﨑 亮, 山口 浩雄, 樋渡 昭雄, 松下 拓也, 吉良 潤一, Cerebrospinal fluid cytokine levels in multiple system atrophy patients, 第５６回日本神経学会, 2015.05.|
|10.||山﨑 亮, 吉良 潤一, Combined Central and Peripheral Demyelination (CCPD): clinical features and immune mechanisms, East Asia Neurology Forum 2015, 2015.04.|
|11.||山﨑 亮, 河村 信利, 米川 智, 松下 拓也, 村井 弘之, 吉良 潤一, Anti-neurofascin antibody in patients with combined central and peripheral demyelination, ECTRIMS, 2013.10.|
|12.||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.
|13.||The impaired neuroprotective function of microglia in the mutant superoxide dismutase 1 transgenic mice.|
|14.||The impaired neuroprotective function of microglia in the mutant SOD1 transgenic mice.|