机构：[1]Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China[2]Department ofImmunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China[3]Department of Traditional Chinese Medicine,College of Medicine, Xiamen University, Xiamen Fujian 361102, China[4]Ann Romney Center for Neurologic Diseases, Brigham andWomen's Hospital and Harvard MedicalSchool, Boston, MA 02115, USA[5]Teaching Center of Experimental Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou Guangdong510080, China[6]Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Guangdong 510080, China
Rapamycin protects mice against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons, which is an established model for Parkinson's disease. We demonstrated that rapamycin preserves astrocytic expression of glutamate transporters and glutamate reuptake. The protective effect was also observed in astrocyte cultures, indicating that rapamycin acts directly on astrocytes. In the MPTP model, rapamycin caused reduced expression of the E3 ubiquitin ligase Nedd4-2 (neuronal precursor cell expressed developmentally downregulated 4-2) and reduced colocalization of glutamate transporters with ubiquitin. Rapamycin increased interleukin-6 (IL-6) expression, which was associated with reduced expression of inflammatory cytokines, indicating anti-inflammatory properties of IL-6 in the MPTP model. NF-κB was shown to be a key mediator for rapamycin, whereas Janus kinase 2, signal transducer and activator of transcription 3, phosphoinositide 3-kinase, and Akt partially mediated rapamycin effects in astrocytes. These results demonstrate for the first time in a Parkinson's disease animal model that the neuroprotective effects of rapamycin are associated with glial and anti-inflammatory effects.
基金：
This work was supported by grants from the National
Natural Science Foundation of China (Grant Nos 31170734, 31570716, U1603281 to
SQ and 81271428, 81471292, U1503222, 81430021 to PX), the Science and
Technology Planning Project of Guangdong Province (Grant Nos 2012B050200003,
2013B021800305, 2016A050502025 to SQ), the Science and Technology Planning
Project of Guangzhou (Grant No. 2013J4500018 to SQ and 2014J4100008 to XZ),
the Scientific and Technological Innovation Programs of Higher Education Institution
in Guangdong (Grant No. 2013KJCX0041 to SQ), and the Alzheimer’s Association
(NIRG-12-242825 to SL).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|2 区生物
小类|3 区细胞生物学
最新[2025]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China[2]Department ofImmunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China[3]Department of Traditional Chinese Medicine,College of Medicine, Xiamen University, Xiamen Fujian 361102, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China[2]Department ofImmunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China[4]Ann Romney Center for Neurologic Diseases, Brigham andWomen's Hospital and Harvard MedicalSchool, Boston, MA 02115, USA[6]Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Guangdong 510080, China[*1]Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China.[*2]Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.[*3]Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510080, China
推荐引用方式(GB/T 7714)：
Zhang Yunlong,He Xiaoliang,Wu Xiaojuan,et al.Rapamycin upregulates glutamate transporter and IL-6 expression in astrocytes in a mouse model of Parkinson's disease.[J].Cell death & disease.2017,8(2):e2611.doi:10.1038/cddis.2016.491.
APA：
Zhang Yunlong,He Xiaoliang,Wu Xiaojuan,Lei Ming,Wei Zhiyun...&Qu Shaogang.(2017).Rapamycin upregulates glutamate transporter and IL-6 expression in astrocytes in a mouse model of Parkinson's disease..Cell death & disease,8,(2)
MLA：
Zhang Yunlong,et al."Rapamycin upregulates glutamate transporter and IL-6 expression in astrocytes in a mouse model of Parkinson's disease.".Cell death & disease 8..2(2017):e2611
生物学