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研究光照对多巴胺能神经元的有害影响的体外方法。

In-vitro Approaches to Investigate the Detrimental Effect of Light on Dopaminergic Neurons.

机构信息

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.

出版信息

Neuroscience. 2024 Apr 19;544:104-116. doi: 10.1016/j.neuroscience.2024.01.009. Epub 2024 Jan 18.

DOI:10.1016/j.neuroscience.2024.01.009
PMID:38244669
Abstract

Our recent study revealed that fluorescent lamp light can penetrate deep into the brain of mice and rats leading to the development of typical histological characteristics associated with Parkinson's disease such as the loss of dopamine neurons in the substantia nigra. Monochromatic LED lights were thus used in this work to deepen our knowledge on the effects of the major wavelength peaks of fluorescent light on mouse and human dopaminergic cells. In particular, we exposed immortalized dopaminergic MN9D neuronal cells, primary cultures of mouse mesencephalic dopaminergic cells and human dopaminergic neurons differentiated from induced pluripotent stem cells (hiPSC) to different LED light wavelengths. We found that chronic exposure to LED light reduced overall undifferentiated MN9D cell number, with the most significant effects observed at wavelengths of 485 nm and 610 nm. Moreover, LED light especially at 610 nm was able to negatively impact on the survival of mouse mesencephalic dopaminergic cells and of human dopaminergic neurons derived from hiPSC. Notably, differentiated MN9D dopaminergic cells, which closely resemble mature dopamine neuronal phenotype, acutely exposed for 3 h at 610 nm, showed a clear increase in ROS production and cytotoxicity compared to controls undifferentiated MN9D cells. These increases were even more pronounced by the co-treatment with the oxidative agent HO. Collectively, these findings suggest that specific wavelengths, particularly those capable of penetrating deep into the brain, could potentially pose an environmental hazard in relation to Parkinson's disease.

摘要

我们最近的研究表明,荧光灯的光线可以穿透老鼠和老鼠的大脑深处,导致与帕金森病相关的典型组织学特征的发展,如黑质中多巴胺神经元的丧失。因此,在这项工作中使用了单色 LED 灯,以加深我们对荧光灯主要波长峰值对小鼠和人类多巴胺能细胞影响的认识。特别是,我们将永生化多巴胺能 MN9D 神经元细胞、小鼠中脑多巴胺能细胞原代培养物和诱导多能干细胞(hiPSC)分化的人类多巴胺能神经元暴露于不同的 LED 光波长下。我们发现,慢性暴露于 LED 光会降低未分化 MN9D 细胞的总数,在 485nm 和 610nm 波长下观察到最显著的影响。此外,LED 光尤其是 610nm 的波长,能够对小鼠中脑多巴胺能细胞和源自 hiPSC 的人类多巴胺能神经元的存活产生负面影响。值得注意的是,与未分化的 MN9D 细胞相比,急性暴露于 610nm 3 小时的分化 MN9D 多巴胺能细胞显示出明显增加的 ROS 产生和细胞毒性。这种增加在与氧化剂 HO 共同处理时更为明显。总之,这些发现表明,特定波长,特别是那些能够穿透大脑深处的波长,可能与帕金森病有关,构成环境危害。

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