Transplantation of platelet-derived mitochondria alleviates cognitive impairment and mitochondrial dysfunction in db/db mice
Transplantation of platelet-derived mitochondria alleviates cognitive impairment and mitochondrial dysfunction in db/db mice
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血小板源性线粒体移植可减轻 db/db 小鼠的认知障碍和线粒体功能障碍
DOI：
10.1042/cs20200530
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发表时间：
2020-08-01
期刊：
影响因子：
6
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
--
作者：
Ma, Hongli;Jiang, Tao;Wang, Qiang
糖尿病相关认知障碍（DACI）可增加主要心血管事件和死亡的风险。神经元功能高度依赖于线粒体，新出现的证据表明，线粒体移植是一种潜在的有效策略，可以减少脑损伤和相关疾病。血小板在血液中含量丰富，可以被认为是小尺寸线粒体的现成来源。这些细胞可以很容易地通过简单的静脉穿刺从外周血中获得，并且入侵很小。本研究旨在探讨血小板源性线粒体（Mito-Pit）移植是否能改善DACI。采用Morris水迷宫试验评估db/db小鼠的认知行为。结果表明，Mito-Plt在脑室内注射24小时后内化到海马神经元。重要的是，Mito-Plt移植1个月后，db/db小鼠的DACI得到缓解，并伴有线粒体数量增加，线粒体功能恢复，氧化应激和神经元凋亡减轻，海马中A β和Tau的积累减少。综上所述，数据表明Mito-Pit移植减轻了db/db小鼠的认知障碍和线粒体功能障碍。该方法可能是一种潜在的治疗应用于DACI的治疗。
Diabetes-associated cognitive impairment (DACI) can increase the risk of major cardiovascular events and death. Neuronal functionality is highly dependent on mitochondria and emerging evidence has shown that mitochondrial transplantation is a potential and effective strategy that can reduce brain injury and associated disorders. Platelets are abundant in blood and can be considered a readily available source of small-size mitochondria. These cells can be easily acquired from the peripheral blood with minimal invasion via simple venipuncture. The present study aimed to investigate whether transplantation of platelet-derived mitochondria (Mito-Pit) could improve DACI. Cognitive behaviors were assessed using the Morris water maze test in db/db mice. The results demonstrated that Mito-Plt was internalized into hippocampal neurons 24 h following intracerebroventricular injection. Importantly, one month following Mito-Plt transplantation, DACI was alleviated in db/db mice and the effect was accompanied with increased mitochondrial number, restored mitochondrial function, attenuated oxidative stress and neuronal apoptosis, as well as decreased accumulation of A beta and Tau in the hippocampus. Taken together, the data demonstrated that transplantation of Mito-Pit attenuated cognitive impairment and mitochondrial dysfunction in db/db mice. This method may be a potential therapeutic application for the treatment of DACI.