Snx27 Deletion Promotes Recovery From Spinal Cord Injury by Neuroprotection and Reduces Macrophage/Microglia Proliferation

被引:7
作者
Zeng, Yuzhe [1 ]
Wang, Nawen [2 ]
Guo, Tiantian [2 ]
Zheng, Qiuyang [2 ]
Wang, Shuang [1 ]
Wu, Songsong [1 ]
Li, Xi [1 ]
Wu, Jin [1 ]
Chen, Zhida [1 ]
Xu, Huaxi [3 ]
Wang, Xin [2 ,4 ]
Lin, Bin [1 ]
机构
[1] Xiamen Univ, Affiliated Southeast Hosp, Dept Orthopaed, Orthopaed Ctr Peoples Liberat Army, Zhangzhou, Peoples R China
[2] Xiamen Univ, Fujian Prov Key Lab Neurodegenerat Dis & Aging Re, Inst Neurosci, Coll Med,Collaborat Innovat Ctr Brain Sci, Xiamen, Peoples R China
[3] Sanford Burnham Prebys Med Discovery Inst, Neurosci Initiat, La Jolla, CA USA
[4] Xiamen Univ, State Key Lab Cellular Stress Biol, Xiamen, Peoples R China
来源
FRONTIERS IN NEUROLOGY | 2018年 / 9卷
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
sorting nexin 27; neuroprotection; macrophage/microglia; functional recovery; spinal cord injury; MICROGLIA ACTIVATION; FUNCTIONAL RECOVERY; MOTOR FUNCTION; CELL-DEATH; PROTEIN; IMPROVES; AXONS; PTEN; INFLAMMATION; CONTRIBUTES;
D O I
10.3389/fneur.2018.01059
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Sorting nexin 27 (SNX27) is an endosome-associated cargo adaptor that is involved in various pathologies and development of neurological diseases. However, the role of SNX27 in spinal cord injury (SCI) remains unclear. In this study, we found that SNX27 was up-regulated in injured mice spinal cords by western blot and immunofluorescence. A comparative analysis of Basso mouse scale (BMS), footprint test and corticospinal tract (CST) tracing in Snx27(+/+) and Snx27(+/-) mice revealed that haploinsufficiency of SNX27 ameliorated the clinical symptoms of SCI. Based on the results of western blot and immunofluorescence, mechanistically, we found that SNX27 deficiency suppresses apoptotic caspase-3 induced neuronal death. In addition, SNX27 haploinsufficiency lowers the infiltration and activation of macrophage/microglia by suppressing their proliferation at the SCI lesion site. Together, these results suggest that down-regulation of SNX27 is a potential therapy targeting both acute neuronal death and chronic neuroinflammation, and promoting nerve repair after SCI.
引用
收藏
页数:11
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