Upregulation of TREM2 attenuates neuroinflammation and dopaminergic neurotoxicity in MPTP model mice with Parkinson disease  

作　　者：REN Man-ru GUO Ying WEI Xin-bing YAN Shao-qi QIN Yue ZHANG Bin LOU Hai-yan 

机构地区：[1]Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China

出　　处：《中国药理学与毒理学杂志》2018年第9期684-684,共1页Chinese Journal of Pharmacology and Toxicology

基　　金：Shandong Province Science and Technology Program (2016GSF201061).

摘　　要：OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying signaling pathway that mediate TREM2 function.METHODS TREM2 adenovirus were stereologically injected into the right striatum.Two weeks later,MPTP was intraperitoneally injected to produce the acute MPTP mouse model of PD.Mice were sacrificed at different time points following MPTP for biochemical or histological study.RESULTS Overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo.Further study revealed that TREM2 may inhibit neuroinflammation by negatively regulating the TRAF6/TLR4-mediated activation of the MAPK and NF-κB signaling pathways.CONCLUSION TREM2 may have important neuroprotective effects against PD by critical y modulating neuroinflammatory responses.OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying signaling pathway that mediate TREM2 function.METHODS TREM2 adenovirus were stereologically injected into the right striatum.Two weeks later,MPTP was intraperitoneally injected to produce the acute MPTP mouse model of PD.Mice were sacrificed at different time points following MPTP for biochemical or histological study.RESULTS Overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo.Further study revealed that TREM2 may inhibit neuroinflammation by negatively regulating the TRAF6/TLR4-mediated activation of the MAPK and NF-κB signaling pathways.CONCLUSION TREM2 may have important neuroprotective effects against PD by critical y modulating neuroinflammatory responses.

关 键 词：triggering receptor expressed on MYELOID cells-2 PARKINSON disease microglia NEUROINFLAMMATION 

分 类 号：R[医药卫生]