Mitochondrial transfer occurs between cells, and it is important for damaged cells to receive healthy mitochondria to maintain their normal function and protect against cell death. Accumulating evidence suggests that the functional mitochondria of astrocytes are released and transferred to oxygen–glucose deprivation/reoxygenation (OGD/R)-injured neurons. Mild hypothermia (33 °C) is capable of promoting this process, which partially restores the function of damaged neurons. However, the pathways and mechanisms by which mild hypothermia facilitates mitochondrial transfer remain unclear. We are committed to studying the role of mild hypothermia in neuroprotection to provide reliable evidences and insights for the clinical application of mild hypothermia in brain protection. Tunneling nanotubes (TNTs) are considered to be one of the routes through which mitochondria are transferred between cells. In this study, an OGD/R-injured neuronal model was successfully established, and TNTs, mitochondria, neurons and astrocytes were double labeled using immunofluorescent probes. Our results showed that TNTs were present and involved in the transfer of mitochondria between cells in the mixed-culture system of neurons and astrocytes. When neurons were subjected to OGD/R exposure, TNT formation and mitochondrial transportation from astrocytes to injured neurons were facilitated. Further analysis revealed that mild hypothermia increased the quantity of astrocytic mitochondria transferred into damaged neurons through TNTs, raised the mitochondrial membrane potential (MMP), and decreased the neuronal damage and death during OGD/R. Altogether, our data indicate that TNTs play an important role in the endogenous neuroprotection of astrocytic mitochondrial transfer. Furthermore, mild hypothermia enhances astrocytic mitochondrial transfer into OGD/R-injured neurons via TNTs, thereby promoting neuroprotection and neuronal recovery.

中文翻译：

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低温促进隧道纳米管形成以及星形胶质细胞线粒体转移到氧糖剥夺/复氧损伤的神经元中

线粒体转移发生在细胞之间，对于受损细胞来说，接受健康的线粒体以维持其正常功能并防止细胞死亡非常重要。越来越多的证据表明，星形胶质细胞的功能性线粒体被释放并转移到氧糖剥夺/复氧（OGD/R）损伤的神经元中。轻度低温（33°C）能够促进这一过程，从而部分恢复受损神经元的功能。然而，亚低温促进线粒体转移的途径和机制仍不清楚。我们致力于研究亚低温在神经保护中的作用，为亚低温脑保护的临床应用提供可靠的证据和见解。隧道纳米管（TNT）被认为是线粒体在细胞之间转移的途径之一。本研究成功建立了OGD/R损伤的神经元模型，并使用免疫荧光探针对TNT、线粒体、神经元和星形胶质细胞进行双标记。我们的结果表明，TNT 存在并参与神经元和星形胶质细胞混合培养系统中细胞之间线粒体的转移。当神经元受到 OGD/R 暴露时，TNT 形成以及线粒体从星形胶质细胞运输到受损神经元的过程得到促进。进一步分析表明，亚低温增加了通过TNT转移到受损神经元中的星形胶质细胞线粒体的数量，提高了线粒体膜电位（MMP），并减少了OGD/R期间的神经元损伤和死亡。总而言之，我们的数据表明 TNT 在星形细胞线粒体转移的内源性神经保护中发挥着重要作用。此外，轻度低温可增强星形细胞线粒体通过 TNT 转移至 OGD/R 损伤的神经元，从而促进神经保护和神经元恢复。