Department of Anesthesiology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China.
Department of Anesthesiology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China.
Brain Res. 2024 May 15;1831:148826. doi: 10.1016/j.brainres.2024.148826. Epub 2024 Feb 23.
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.
线粒体在细胞间发生转移，受损细胞获得健康的线粒体对于维持其正常功能和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葡萄糖剥夺/再复氧（OGD/R）损伤的神经元中。轻度低温（33°C）能够促进这一过程，部分恢复受损神经元的功能。然而，轻度低温促进线粒体转移的途径和机制尚不清楚。我们致力于研究轻度低温在神经保护中的作用，为轻度低温在脑保护中的临床应用提供可靠的证据和见解。隧道纳米管（TNTs）被认为是细胞间线粒体转移的途径之一。在这项研究中，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 TNTs、线粒体、神经元和星形胶质细胞进行了双重标记。结果表明，在神经元和星形胶质细胞混合培养系统中，TNTs 存在并参与了细胞间线粒体的转移。当神经元受到 OGD/R 暴露时，TNT 的形成和线粒体从星形胶质细胞向损伤神经元的运输都得到了促进。进一步的分析表明，轻度低温通过 TNTs 增加了星形胶质细胞向受损神经元转移的线粒体数量，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。总之，我们的数据表明 TNTs 在星形胶质细胞线粒体转移的内源性神经保护中发挥重要作用。此外，轻度低温通过 TNTs 增强了星形胶质细胞向 OGD/R 损伤神经元的线粒体转移，从而促进了神经保护和神经元恢复。
