| Item type |
文献 / Documents(1) |
| 公開日 |
2018-11-12 |
| アクセス権 |
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|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1038/srep40518 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1038/srep40518 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
FcRγ-dependent immune activation initiates astrogliosis during the asymptomatic phase of Sandhoff disease model mice |
|
言語 |
en |
| 著者 |
オガワ, ヤスヒロ
サノ, タカフミ
イリサ, マサヒロ
コダマ, タカシ
サイトウ, タカヒロ
フルサワ, エイリ
カイヅ, カツトシ
ヤナギ, ユウスケ
ツキムラ, タカヒロ
トガワ, タダヤス
ヤマナカ, ショウジ
伊藤, 孝司
サクラバ, ヒトシ
オオイシ, カズヒコ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Sandhoff disease (SD) is caused by the loss of β-hexosaminidase (Hex) enzymatic activity in lysosomes resulting from Hexb mutations. In SD patients, the Hex substrate GM2 ganglioside accumulates abnormally in neuronal cells, resulting in neuronal loss, microglial activation, and astrogliosis. Hexb−/− mice, which manifest a phenotype similar to SD, serve as animal models for examining the pathophysiology of SD. Hexb−/− mice reach ~8 weeks without obvious neurological defects; however, trembling begins at 12 weeks and is accompanied by startle reactions and increased limb tone. These symptoms gradually become severe by 16–18 weeks. Immune reactions caused by autoantibodies have been recently associated with the pathology of SD. The inhibition of immune activation may represent a novel therapeutic target for SD. Herein, SD mice (Hexb−/−) were crossed to mice lacking an activating immune receptor (FcRγ−/−) to elucidate the potential relationship between immune responses activated through SD autoantibodies and astrogliosis. Microglial activation and astrogliosis were observed in cortices of Hexb−/− mice during the asymptomatic phase, and were inhibited in Hexb−/− FcRγ−/− mice. Moreover, early astrogliosis and impaired motor coordination in Hexb−/− mice could be ameliorated by immunosuppressants, such as FTY720. Our findings demonstrate the importance of early treatment and the therapeutic effectiveness of immunosuppression in SD. |
|
言語 |
en |
| 書誌情報 |
en : Scientific Reports
巻 7,
p. 40518,
発行日 2017-01-13
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20452322 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 備考 |
|
|
言語 |
ja |
|
値 |
Supplementary Information : srep_7_40518_s1.pdf |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| EID |
|
|
識別子 |
339728 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
srep_7_40518.pdf (6.74 MB)
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