GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities
文献类型：期刊论文
| 作者 | Yang, Xinying4,5; Zhangyi, Zhongheng3; Yu, Aisong5; Zhou, Qinming3; Xia, Aihua4; Qiu, Ji4; Cai, Meixiang4; Chu, Xingkun4; Li, Liang4; Feng, Zhengnan4 |
| 刊名 | CNS NEUROSCIENCE & THERAPEUTICS
 |
| 出版日期 | 2024-07-01 |
| 卷号 | 30期号:7页码:15 |
| 关键词 | gut microbiota GV-971 neuroinflammation Neuromyelitis optica spectrum disorders NMO-IgG |
| ISSN号 | 1755-5930 |
| DOI | 10.1111/cns.14847 |
| 通讯作者 | Chen, Sheng(mztcs@163.com) ; Xie, Zuoquan(zqxie@simm.ac.cn) |
| 英文摘要 | Aims: Growing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV-971 in NMOSD. GV-971 is a drug used for treating mild-to-moderate Alzheimer's disease, which targets the gut-brain axis and reduces neuroinflammation. Methods: To evaluate GV-971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO-IgG into aged mice (11 months old) or using NMO-IgG along with complement injection and microbubble-enhanced low-frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV-971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis. Results: Our findings indicated that GV-971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders. Conclusions: GV-971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders. |
| WOS关键词 | OLIGOSACCHARIDE SUGAR CHAIN ; T-CELLS ; MULTIPLE-SCLEROSIS ; ACIDIC OLIGOSACCHARIDE ; SPECTRUM ; AQUAPORIN-4 ; EXPRESSION ; HEALTH ; IGG |
| 资助项目 | Lingang Laboratory[LG202101-01-01] ; Shandong Laboratory Program[SYS202205] ; Natural Science Foundation of China for Innovation Research Group[81821005] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001264878800001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312258]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Sheng; Xie, Zuoquan |
| 作者单位 | 1.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China 2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China 3.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Neurol, Shanghai 200025, Peoples R China 4.Shanghai Green Valley Pharmaceut Co Ltd, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Xinying,Zhangyi, Zhongheng,Yu, Aisong,et al. GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities[J]. CNS NEUROSCIENCE & THERAPEUTICS,2024,30(7):15. |
| APA | Yang, Xinying.,Zhangyi, Zhongheng.,Yu, Aisong.,Zhou, Qinming.,Xia, Aihua.,...&Xie, Zuoquan.(2024).GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities.CNS NEUROSCIENCE & THERAPEUTICS,30(7),15. |
| MLA | Yang, Xinying,et al."GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities".CNS NEUROSCIENCE & THERAPEUTICS 30.7(2024):15. |
入库方式： OAI收割
来源：上海药物研究所
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