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缩醛磷脂可改善小鼠脑内β淀粉样蛋白的淋巴清除及认知功能。

Plasmalogens Improve Lymphatic Clearance of Amyloid Beta from Mouse Brain and Cognitive Functions.

作者信息

Shirokov Alexander, Zlatogosrkaya Daria, Adushkina Viktoria, Vodovozova Elena, Kardashevskaya Kristina, Sultanov Ruslan, Kasyanov Sergey, Blokhina Inna, Terskov Andrey, Tzoy Maria, Evsyukova Arina, Dubrovsky Alexander, Tuzhilkin Matvey, Elezarova Inna, Dmitrenko Alexander, Manzhaeva Maria, Krupnova Valeria, Semiachkina-Glushkovskaia Anastasiia, Ilyukov Egor, Myagkov Dmitry, Tuktarov Dmitry, Popov Sergey, Inozemzev Tymophey, Navolokin Nikita, Fedosov Ivan, Semyachkina-Glushkovskaya Oxana

机构信息

Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Prospekt Entuziastov 13, 410049 Saratov, Russia.

Department of Biology, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov, Russia.

出版信息

Int J Mol Sci. 2024 Nov 22;25(23):12552. doi: 10.3390/ijms252312552.

Abstract

Amyloid beta (Aβ) is a neuronal metabolic product that plays an important role in maintaining brain homeostasis. Normally, intensive brain Aβ formation is accompanied by its effective lymphatic removal. However, the excessive accumulation of brain Aβ is observed with age and during the development of Alzheimer's disease (AD) leading to cognitive impairment and memory deficits. There is emerging evidence that plasmalogens (Pls), as one of the key brain lipids, may be beneficial for AD and cognitive aging. Here, we studied the effects of Pls on cognitive functions and the lymphatic clearance of Aβ from the brain of AD mice and mice of different ages. The results showed that Pls effectively reduce brain Aβ levels and facilitate learning in aged but not old mice. In AD mice, Pls improve the lymphatic clearance of Aβ that is accompanied by an increase in general motor activity and an improvement of the emotional status and learning ability. Thus, these findings suggest that Pls could be a promising candidate for the alternative or concomitant therapy of AD and age-related brain diseases to enhance the lymphatic clearance of Aβ from the brain and cognitive functions.

摘要

β-淀粉样蛋白(Aβ)是一种神经元代谢产物,在维持大脑内环境稳定中发挥重要作用。正常情况下,大脑中Aβ的大量形成伴随着其通过淋巴系统的有效清除。然而,随着年龄增长以及在阿尔茨海默病(AD)发展过程中,会观察到大脑中Aβ的过度积累,从而导致认知障碍和记忆缺陷。越来越多的证据表明,缩醛磷脂(Pls)作为大脑中的关键脂质之一,可能对AD和认知衰老有益。在此,我们研究了Pls对AD小鼠和不同年龄小鼠认知功能以及大脑中Aβ淋巴清除的影响。结果表明,Pls能有效降低老年小鼠而非老龄小鼠大脑中的Aβ水平,并促进其学习能力。在AD小鼠中,Pls改善了Aβ的淋巴清除,同时伴有总体运动活动增加、情绪状态和学习能力改善。因此,这些发现表明,Pls可能是AD和年龄相关脑部疾病替代或联合治疗的有前景候选药物,可增强大脑中Aβ的淋巴清除和认知功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f6/11640916/f05529ad1fe4/ijms-25-12552-g001.jpg

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