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硫酸镁对6-羟基多巴胺诱导的帕金森病大鼠视网膜多巴胺能神经元的神经保护和抗焦虑作用:一项初步研究。

The Neuroprotective and Anxiolytic Effects of Magnesium Sulfate on Retinal Dopaminergic Neurons in 6-OHDA-Induced Parkinsonian Rats: A Pilot Study.

作者信息

Huang Leyi, Lin Renxi, Zhang Chunying, Zheng Shaoqing, Wang Yiyang, Wu Zeyu, Chen Sihao, Shen Yihan, Zhang Guoheng, Qi Yuanlin, Lin Ling

机构信息

Department of Biochemistry and Molecular Biology, Fujian Medical University, Fuzhou 350122, China.

Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Medical University, Fuzhou 350122, China.

出版信息

Brain Sci. 2024 Aug 26;14(9):861. doi: 10.3390/brainsci14090861.

Abstract

This study investigates the protective effects of magnesium sulfate on dopamine neurons in the retinas of rats with 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Rapidly progressing cognitive decline often precedes or coincides with the motor symptoms associated with PD. PD patients also frequently exhibit visual function abnormalities. However, the specific mechanisms underlying visual dysfunction in PD patients are not yet fully understood. Therefore, this study aims to investigate whether magnesium homeostasis affects dopaminergic neurons in the retina of PD rats. Thirty-six rats were divided into four groups: (1) control, (2) control with magnesium sulfate (control/MgSO), (3) Parkinson's disease (PD), and (4) Parkinson's disease with magnesium sulfate (PD/MgSO). The apomorphine-induced (APO) rotation test assessed the success of the PD models. The open-field experiment measured the rats' anxiety levels. Tyrosine hydroxylase (TH) and glutamate levels, indicators of dopamine neuron survival, were detected using immunofluorescence staining. Protein levels of solute carrier family 41 A1 (SCL41A1), magnesium transporter 1 (MagT1), and cyclin M2 (CNNM2) in the retina were analyzed using Western blot. Results showed that, compared to the PD group, rats in the PD/MgSO group had improved psychological states and motor performance at two and four weeks post-surgery. The PD/MgSO group also exhibited significantly higher TH fluorescence intensity in the left retinas and lower glutamate fluorescence intensity than the PD group. Additional experiments indicated that the protein levels of SLC41A1, MagT1, and CNNM2 were generally higher in the retinas of the PD/MgSO group, along with an increase in retinal magnesium ion content. This suggests that magnesium sulfate may reduce glutamate levels and protect dopamine neurons in the retina. Thus, magnesium sulfate might have therapeutic potential for visual functional impairments in PD patients.

摘要

本研究调查硫酸镁对6-羟基多巴胺(6-OHDA)诱导的帕金森病(PD)大鼠视网膜中多巴胺能神经元的保护作用。快速进展的认知衰退通常先于或与PD相关的运动症状同时出现。PD患者也经常表现出视觉功能异常。然而,PD患者视觉功能障碍的具体机制尚未完全明确。因此,本研究旨在探讨镁稳态是否影响PD大鼠视网膜中的多巴胺能神经元。36只大鼠被分为四组:(1)对照组,(2)硫酸镁对照组(对照/MgSO),(3)帕金森病组(PD),以及(4)硫酸镁治疗的帕金森病组(PD/MgSO)。阿扑吗啡诱导(APO)旋转试验评估PD模型的成功与否。旷场实验测量大鼠的焦虑水平。使用免疫荧光染色检测酪氨酸羟化酶(TH)和谷氨酸水平,这是多巴胺能神经元存活的指标。使用蛋白质印迹法分析视网膜中溶质载体家族41 A1(SCL41A1)、镁转运蛋白1(MagT1)和细胞周期蛋白M2(CNNM2)的蛋白质水平。结果显示,与PD组相比,PD/MgSO组大鼠在手术后两周和四周时心理状态和运动表现有所改善。PD/MgSO组左侧视网膜中TH荧光强度也显著高于PD组,而谷氨酸荧光强度则较低。进一步实验表明,PD/MgSO组视网膜中SLC41A1、MagT1和CNNM2的蛋白质水平总体较高,同时视网膜镁离子含量增加。这表明硫酸镁可能降低谷氨酸水平并保护视网膜中的多巴胺能神经元。因此,硫酸镁可能对PD患者的视觉功能损害具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5382/11430011/645daedfe1e5/brainsci-14-00861-g001.jpg

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