Institute of Cell Biophysics of the Russian Academy of Sciences-Federal Research Center, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia.
Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia.
Exp Biol Med (Maywood). 2022 Mar;247(5):416-425. doi: 10.1177/15353702211056866. Epub 2021 Nov 2.
Here, we found that functionally active mitochondria isolated from the brain of NMRI donor mice and administrated intranasally to recipient mice penetrated the brain structures in a dose-dependent manner. The injected mitochondria labeled with the MitoTracker Red localized in different brain regions, including the neocortex and hippocampus, which are responsible for memory and affected by degeneration in patients with Alzheimer's disease. In behavioral experiments, intranasal microinjections of brain mitochondria of native NMRI mice improved spatial memory in the olfactory bulbectomized (OBX) mice with Alzheimer's type degeneration. Control OBX mice demonstrated loss of spatial memory tested in the Morris water maze. Immunocytochemical analysis revealed that allogeneic mitochondria colocalized with the markers of astrocytes and neurons in hippocampal cell culture. The results suggest that a non-invasive route intranasal administration of mitochondria may be a promising approach to the treatment of neurodegenerative diseases characterized, like Alzheimer's disease, by mitochondrial dysfunction.
在这里，我们发现从 NMRI 供体小鼠大脑中分离出的功能活跃的线粒体经鼻内给药后，以剂量依赖的方式穿透脑组织。用 MitoTracker Red 标记的注射线粒体定位于不同的脑区，包括负责记忆并受阿尔茨海默病患者退化影响的新皮质和海马区。在行为实验中，经鼻内微注射天然 NMRI 小鼠的脑线粒体可改善具有阿尔茨海默病样退化的嗅球切除术（OBX）小鼠的空间记忆。对照 OBX 小鼠在 Morris 水迷宫中测试显示出空间记忆丧失。免疫细胞化学分析显示，同种异体线粒体与海马细胞培养中星形胶质细胞和神经元的标志物共定位。结果表明，非侵入性的鼻内给予线粒体可能是治疗以线粒体功能障碍为特征的神经退行性疾病（如阿尔茨海默病）的有前途的方法。
