Cell type- and region-specific translatomes in an MPTP mouse model of Parkinson's disease

被引:5
作者
Huang, Qiaoying [1 ,2 ]
Chen, Congmin [1 ,2 ]
Chen, Weizhao [3 ,4 ,5 ]
Cai, Chaoyu [1 ,2 ]
Xing, Hailin [1 ,2 ]
Li, Junyu [1 ,2 ]
Li, Mingtao [1 ,2 ]
Ma, Shanshan [1 ,2 ]
机构
[1] Sun Yat sen Univ, Zhongshan Sch Med, Guangdong Prov Key Lab Brain Funct & Dis, 74 Zhongshan 2nd Rd, Guangzhou 510080, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, 74 Zhongshan 2nd Rd, Guangzhou 510080, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Hepat Surg, Guangzhou 510630, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 3, Liver Transplantat Ctr, Guangzhou 510630, Peoples R China
[5] Sun Yat Sen Univ, Organ Transplantat Inst, Guangzhou 510630, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
Parkinson's disease; Translatome; RiboTag; Glycosphingolipid; DOPAMINERGIC NEURODEGENERATION; AFFINITY PURIFICATION; MESSENGER-RNA; CONTRIBUTES; ACTIVATION; EXPRESSION; APOPTOSIS; RIBOTAG; GENE; DNA;
D O I
10.1016/j.nbd.2023.106105
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized by the progressive loss of nigrostriatal dopaminergic neurons (DANs), involving the dysregulation of both neurons and glial cells. Cell type- and region-specific gene expression profiles can provide an effective source for revealing the mechanisms of PD. In this study, we adopted the RiboTag approach to obtain cell type (DAN, microglia, astrocytes)- and brain region (substantia nigra, caudate-putamen)-specific translatomes at an early stage in an MPTP-induced mouse model of PD. Through DAN-specific translatome analysis, the glycosphingolipid biosynthetic process was identified as a significantly downregulated pathway in the MPTP-treated mice. ST8Sia6, a key downregulated gene related to glycosphingolipid biosynthesis, was confirmed to be downregulated in nigral DANs from postmortem brains of patients with PD. Specific expression of ST8Sia6 in DANs exerts antiinflammatory and neuroprotective effects in MPTP-treated mice. Through cell type (microglia vs. astrocyte) and brain region (substantia nigra vs. caudate-putamen) comparisons, nigral microglia showed the most intense immune responses. Microglia and astrocytes in the substantia nigra showed similar levels of activation in interferon-related pathways and interferon gamma (IFNG) was identified as the top upstream regulator in both cell types. This work highlights that the glycosphingolipid metabolism pathway in the DAN is involved in neuroinflammation and neurodegeneration in an MPTP mouse model of PD and provides a new data source for elucidating the pathogenesis of PD.
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页数:15
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