MPP+ decreases store-operated calcium entry and TRPC1 expression in Mesenchymal Stem Cell derived dopaminergic neurons.
MPP+ decreases store-operated calcium entry and TRPC1 expression in Mesenchymal Stem Cell derived dopaminergic neurons.
复制标题
MPP 减少间充质干细胞衍生的多巴胺能神经元中钙库操纵的钙进入和 TRPC1 表达。
DOI：
10.1038/s41598-018-29528-x
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发表时间：
2018
影响因子：
4.6
通讯作者：
Ohm,JoyceE
中科院分区：
文献类型：
--
作者：
Sun,Yuyang;Selvaraj,Senthil;Pandey,Sumali;Humphrey,KristenM;Foster,JamesD;Wu,Min;Watt,JohnA;Singh,BrijB;Ohm,JoyceE
帕金森病是一种神经退行性疾病，涉及多巴胺能神经元 (DN) 进行性丧失，目前可用的治疗方法（例如左旋多巴）只能缓解部分症状。干细胞替代对于 PD 患者来说是一种有吸引力的治疗选择，通过在体外条件下分化患者特异性干细胞而衍生的 DN 可能为替代垂死神经元提供了可行的机会。我们采用了之前发表的方法，使用涉及 FGF-2、bFGF、SHH 配体和 BDNF 的 12 天方案将间充质干细胞 (MSC) 分化为 DN。虽然 MSC 衍生的 DN 已被表征为神经元标记和电生理特性，但我们研究了这些 DN 在正常条件下以及暴露于环境神经毒素 1-甲基，4-苯基吡啶鎓离子 (MPP+) 时的钙池操纵钙内流 (SOCE) 机制。总体而言，我们表明 MSC 衍生的 DN 在 SOCE 机制方面具有功能，并且 MPP+暴露会失调钙信号传导，使它们容易受到神经退行性变的影响。由于 MSC 体外分化为 DN 是 PD 疾病建模和再生医学的重要工具，因此本研究的结果可能有助于了解 PD 的病理机制。
Parkinson’s disease is a neurodegenerative disorder involving the progressive loss of dopaminergic neurons (DNs), with currently available therapeutics, such as L-Dopa, only able to relieve some symptoms. Stem cell replacement is an attractive therapeutic option for PD patients, and DNs derived by differentiating patient specific stem cells under definedin-vitroconditions may present a viable opportunity to replace dying neurons. We adopted a previously published approach to differentiate Mesenchymal Stem Cells (MSCs) into DN using a 12-day protocol involving FGF-2, bFGF, SHH ligand and BDNF. While MSC-derived DNs have been characterized for neuronal markers and electrophysiological properties, we investigated store-operated calcium entry (SOCE) mechanisms of these DNs under normal conditions, and upon exposure to environmental neurotoxin, 1-methyl, 4-phenyl pyridinium ion (MPP+). Overall, we show that MSC-derived DNs are functional with regard to SOCE mechanisms, and MPP+exposure dysregulates calcium signaling, making them vulnerable to neurodegeneration. Sincein-vitrodifferentiation of MSCs into DNs is an important vehicle for PD disease modeling and regenerative medicine, the results of this study may help with understanding of the pathological mechanisms underlying PD.