GPR139激动剂对原发性多巴胺能中脑神经元的保护作用支持MPP(+)和鱼藤酮毒性的不同机制。

Protection of Primary Dopaminergic Midbrain Neurons by GPR139 Agonists Supports Different Mechanisms of MPP(+) and Rotenone Toxicity.

作者信息

Bayer Andersen Kirsten, Leander Johansen Jens, Hentzer Morten, Smith Garrick Paul, Dietz Gunnar P H

机构信息

Department of Neurodegeneration, H. Lundbeck A/S Valby, Denmark.

Department of Molecular Screening, H. Lundbeck A/S Valby, Denmark.

出版信息

Front Cell Neurosci. 2016 Jun 28;10:164. doi: 10.3389/fncel.2016.00164. eCollection 2016.

The G-protein coupled receptor 139 (GPR139) is expressed specifically in the brain in areas of relevance for motor control. GPR139 function and signal transduction pathways are elusive, and results in the literature are even contradictory. Here, we examined the potential neuroprotective effect of GPR139 agonism in primary culture models of dopaminergic (DA) neuronal degeneration. We find that in vitro GPR139 agonists protected primary mesencephalic DA neurons against 1-methyl-4-phenylpyridinium (MPP(+))-mediated degeneration. Protection was concentration-dependent and could be blocked by a GPR139 antagonist. However, the protection of DA neurons was not found against rotenone or 6-hydroxydopamine (6-OHDA) mediated degeneration. Our results support differential mechanisms of toxicity for those substances commonly used in Parkinson's disease (PD) models and potential for GPR139 agonists in neuroprotection.

G蛋白偶联受体139（GPR139）在大脑中与运动控制相关的区域特异性表达。GPR139的功能和信号转导途径尚不明确，文献中的结果甚至相互矛盾。在此，我们在多巴胺能（DA）神经元变性的原代培养模型中研究了GPR139激动作用的潜在神经保护作用。我们发现，体外GPR139激动剂可保护原代中脑DA神经元免受1-甲基-4-苯基吡啶鎓（MPP(+)）介导的变性。保护作用呈浓度依赖性，且可被GPR139拮抗剂阻断。然而，未发现DA神经元对鱼藤酮或6-羟基多巴胺（6-OHDA）介导的变性有保护作用。我们的结果支持帕金森病（PD）模型中常用的那些物质的不同毒性机制，以及GPR139激动剂在神经保护方面的潜力。