Magnetic Fields and Magnetically Stimulated Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Differentially Modulate L-Type Voltage-Gated Calcium Channel Activity in Midbrain Neurons
Magnetic Fields and Magnetically Stimulated Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Differentially Modulate L-Type Voltage-Gated Calcium Channel Activity in Midbrain Neurons
复制标题
DOI：
10.1021/acsanm.1c02665
复制
发表时间：
2022-01-05
影响因子：
5.9
通讯作者：
Wang，Ya
中科院分区：
文献类型：
--
作者：
Yuan，Muzhaozi;Bancroft，Eric A.;Wang，Ya
纳米粒子（NPs）在磁刺激过程中产生局部磁力，从而调节神经元的兴奋性并调节神经元的下游信号传导。在静磁场刺激下，包覆金的超顺磁性氧化铁（Au-SPIO）核壳纳米颗粒（NPs）可以促进和引导神经突生长方向。受这些有希望的结果的启发，本研究探讨了Au-SPIO上的SMS （SMS-Au-SPIO）如何影响中脑神经元的生理。透射电子显微镜（TEM）显示，采用羟胺辅助种子生长法在SPIO表面形成Au层制备的Au-SPIO NPs为准球形，直径为20±4 nm。我们发现SMS增强了Au-SPIO的细胞内摄取，并且SMS-Au-SPIO导致中脑神经元l型电压门控Ca2+通道（VGCC）的延迟阻断。具体而言，暴露于SMS或Au-SPIO或SMS-Au-SPIO的中脑神经元中，自发l型vgcc诱导的Ca2+通量的频率显着降低。对Ca2+通量的功率谱密度分析表明，在l型VGCC阻断前后，SMS降低了Ca2+通量幅值（<0.1 Hz）。相比之下，只有在l型VGCC阻断后，SMS-Au-SPIO才能降低Ca2+通量振幅，这表明SMS-Au-SPIO可以调节l型VGCC。最后，SMS单独诱导多巴胺能（DA）神经元凋亡，而SMS- au - spio则没有。因此，SMS和SMS- au - spio对l型vgc介导的Ca2+通量和中脑神经元下游凋亡信号的调节存在差异，这意味着SMS- au - spio可能作为一种药物递送策略应用于治疗帕金森病。
Nanoparticles (NPs) generate localized magnetic forces during magnetic stimulation, which can, in turn, modulate neuronal excitability and regulate downstream signaling in neurons. In agreement with this idea, under static magnetic field stimulation (SMS), gold-coated superparamagnetic iron oxide (Au-SPIO) core–shell nanoparticles (NPs) can promote and guide the direction of neurite outgrowth. Inspired by these promising results, this study investigates how SMS on Au-SPIO (SMS-Au-SPIO) affects the physiology of midbrain neurons. Transmission electron microscopy (TEM) images showed quasispherical shapes and a diameter of 20 ± 4 nm of Au-SPIO NPs synthesized by forming an Au layer on SPIO using a hydroxylamine hydrochloride-assisted seed growth method. We found that SMS enhanced intracellular uptake of Au-SPIO and that SMS-Au-SPIO resulted in a delayed blockade of an L-type voltage-gated Ca2+channel (VGCC) in midbrain neurons. Specifically, the frequency of spontaneous L-type VGCC-induced Ca2+fluxes was significantly reduced in midbrain neurons exposed to either SMS or Au-SPIO or SMS-Au-SPIO. A power spectrum density analysis of Ca2+fluxes showed that SMS decreased Ca2+fluxes amplitudes (<0.1 Hz) before and after L-type VGCC blockade. By contrast, SMS-Au-SPIO decreased Ca2+flux amplitudes only after L-type VGCC blockade, suggesting a modulation of L-type VGCC by SMS-Au-SPIO. Finally, while SMS alone induced apoptosis of dopaminergic (DA) neurons, SMS-Au-SPIO did not. Thus, SMS and SMS-Au-SPIO differentially modulate L-type VGCC-mediated Ca2+fluxes, and downstream apoptotic signaling in midbrain neurons, implying the possible application of SMS-Au-SPIO as a drug delivery strategy to treat Parkinson’s disease.