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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

普瑞巴林治疗不会影响 5XFAD 小鼠的淀粉样蛋白病理学

卷 18, 期 4, 2021

发表于: 08 September, 2021

页: [283 - 297] 页: 15

弟呕挨: 10.2174/1567205018666210713125333

open access plus

摘要

背景：已提出钙失调在阿尔茨海默病病理学的发展中起致病作用。普瑞巴林是一种已获准用于人类使用的化合物，作为处方药 Lyrica 销售。它结合 P/Q 型电压门控钙通道的 α2-δ 亚基，降低钙内流，为癫痫和神经性疼痛提供有效治疗。目的：我们假设淀粉样斑块附近神经元过程中静息钙的增加在神经炎性营养不良的发展和淀粉样蛋白病理的进一步进展中起作用。

方法：5XFAD 小鼠用普瑞巴林口服治疗 12 周，然后使用免疫印迹和免疫荧光成像来量化普瑞巴林与安慰剂治疗小鼠相比的神经炎性营养不良和淀粉样蛋白沉积。

结果：治疗没有降低神经炎性营养不良或淀粉样蛋白沉积的标志物。在逐个斑块的基础上对神经炎性营养不良的图像分析显示，在普瑞巴林治疗的小鼠皮层中面积为 50-450 μm2 的斑块中，LAMP1 与 Aβ42 的相对比例略有非显着增加。此外，测量的普瑞巴林脑浓度与皮质中 BACE1 和 Aβ 的相对水平之间存在统计学上显着的正相关。在海马体中没有观察到这种关系，与安慰剂相比，普瑞巴林治疗的小鼠的平均 Aβ 水平没有增加。我们证实了之前的研究结果，即较小的淀粉样斑块与更大程度的神经炎性营养不良相关。

结论：普瑞巴林可能对 Aβ 有影响，值得进一步研究，但我们的研究并未表明普瑞巴林对淀粉样蛋白病理学有实质性影响。

关键词: 阿尔茨海默氏症、淀粉样蛋白、普瑞巴林、合成、BACE1、营养不良性神经突、钙、5XFAD。

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