Mitochondria transplantation protects traumatic brain injury via promoting neuronal survival and astrocytic BDNF
Mitochondria transplantation protects traumatic brain injury via promoting neuronal survival and astrocytic BDNF
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DOI：
10.1016/j.trsl.2021.03.017
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发表时间：
2021-07-29
影响因子：
7.8
通讯作者：
Wang, Yazhou
中科院分区：
文献类型：
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作者：
Zhao, Jiqian;Qu, Dujie;Wang, Yazhou
创伤性脑损伤（TBI）是世界范围内残疾和瘫痪的主要原因之一。以进行性神经元丢失和星形胶质细胞增生为特征的继发性损伤在脑外伤后认知功能障碍和情绪障碍中起重要作用。然而，目前仍缺乏有效的治疗方法，尤其是手术干预。近年来，线粒体细胞间转移的研究表明，线粒体移植对TBI具有潜在的治疗价值，但尚未得到证实。在本研究中，我们证明了线粒体的快速功能障碍，Tom20在受损皮层中的上调以及随后的认知和情绪障碍。我们的数据表明，来自同种异体肝脏或自体肌肉的线粒体刺激脑实质中类似的小胶质细胞活化。体外实验表明，外源性线粒体可以很容易地内化的神经元，星形胶质细胞和小胶质细胞，少突胶质细胞除外。线粒体移植可有效地挽救神经细胞凋亡，恢复Tom20的表达和JNK的磷酸化。进一步的分析显示，线粒体移植在损伤的皮层诱导了反应性星形胶质细胞中BDNF的显著上调，改善了动物的空间记忆，减轻了焦虑。总之，我们的数据表明，线粒体移植与手术联合可能具有临床转化为TBI治疗的潜力。
Traumatic brain injury (TBI) is one of the leading causes of disability and paralysis around the world. Secondary injury, characterized by progressive neuronal loss and astrogliosis, plays important roles in the post-TBI cognitive impairment and mood disorder. Unfortunately, there still lacks effective treatments, particularly surgery interferences for it. Recent findings of intercellular mitochondria transfer implies a potential therapeutic value of mitochondria transplantation for TBI, which has not been tested yet. In the present study, we demonstrated a quick dysfunction of mitochondria, up-regulation of Tom20 in the injured cortex and subsequent cognitive and mood impairment. Our data demonstrated that mitochondria derived from allogeneic liver or autogeneic muscle stimulated similar microglial activation in brain parenchyma. In vitro experiments showed that exogenous mitochondria could be easily internalized by neurons, astrocytes, and microglia, except for oligodendrocytes. Mitochondria transplantation effectively rescued neuronal apoptosis, restored the expression of Tom20 and the phosphorylation of JNK. Further analysis revealed that mitochondria transplantation in injured cortex induced a significant up-regulation of BDNF in reactive astrocytes, improved animals' spatial memory and alleviated anxiety. In together, our data indicate that mitochondria transplantation may has the potential of clinical translation for TBI treatment, in combination with surgery.