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低中剂量全脑 γ 射线照射调节 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠模型中胶质纤维酸性蛋白和细胞间黏附分子-1 的表达。

Low-moderate dose whole-brain γ-ray irradiation modulates the expressions of glial fibrillary acidic protein and intercellular adhesion molecule-1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model.

机构信息

Radiological and Medical Support Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.

Radiological and Medical Support Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea; Division of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.

出版信息

Neurobiol Aging. 2023 Dec;132:175-184. doi: 10.1016/j.neurobiolaging.2023.06.015. Epub 2023 Jun 29.

Abstract

The anti-inflammatory efficacy of radiation therapy (RT) with single fractions below 1.0 Gy has been demonstrated in Alzheimer's disease mouse models. As neuroinflammation is also a major pathological feature of Parkinson's disease (PD), RT may also be effective in PD treatment. Therefore, this study aimed to investigate the anti-inflammatory effect of low-moderate dose RT (LMDRT, 0.6 Gy/single dose, for 5 days) exposure in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally, for 5 consecutive days)-induced PD mouse model. Importantly, LMDRT reduced the levels of glial fibrillary acidic protein and intercellular adhesion molecule-1 (CD54) in the striatum region, which increased following MPTP administration. LMDRT also modulated inflammatory gene expression patterns in the substantia nigra region of the MPTP-treated mice. However, LMDRT had no direct effects on the severe loss of dopaminergic neurons and impaired motor behavior in the rotarod test. These results indicate that LMDRT has anti-inflammatory effects by modulating neuroinflammatory factors, including glial fibrillary acidic protein and intercellular adhesion molecule-1, but showed no behavioral improvements or neuroprotection in the MPTP-induced mouse model of PD.

摘要

单次低于 1.0Gy 的放射治疗(RT)的抗炎疗效已在阿尔茨海默病小鼠模型中得到证实。由于神经炎症也是帕金森病(PD)的主要病理特征,RT 也可能对 PD 的治疗有效。因此,本研究旨在探讨低中度剂量 RT(LMDRT,单次剂量 0.6Gy,连续 5 天)暴露在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP;30mg/kg,腹腔内,连续 5 天)诱导的 PD 小鼠模型中的抗炎作用。重要的是,LMDRT 降低了纹状体区域中胶质纤维酸性蛋白和细胞间黏附分子-1(CD54)的水平,而 MPTP 给药后这些蛋白的水平增加。LMDRT 还调节了 MPTP 处理的小鼠黑质区域中的炎症基因表达模式。然而,LMDRT 对旋转棒测试中严重的多巴胺能神经元丧失和运动行为障碍没有直接影响。这些结果表明,LMDRT 通过调节神经炎症因子(包括胶质纤维酸性蛋白和细胞间黏附分子-1)具有抗炎作用,但在 MPTP 诱导的 PD 小鼠模型中未显示出行为改善或神经保护作用。

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