Chronic intermittent hypoxia alters the dendritic mitochondrial structure and activity in the pre-Botzinger complex of rats
Chronic intermittent hypoxia alters the dendritic mitochondrial structure and activity in the pre-Botzinger complex of rats
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DOI：
10.1096/fj.201902141r
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发表时间：
2020-09-10
期刊：
影响因子：
4.8
通讯作者：
Liu, Ying-Ying
中科院分区：
文献类型：
--
作者：
Kang, Jun-Jun;Fung, Man-Lung;Liu, Ying-Ying
线粒体生物能量学与神经元活动动态耦合，神经元活动被缺氧诱导的呼吸神经可塑性改变。在这里，我们报告了接受慢性间歇性缺氧（CIH）模拟严重阻塞性睡眠呼吸暂停的大鼠的前Botzinger复合体（pre-BotC）中突触后线粒体的结构特征。通过神经激肽1受体的免疫反应性，检测了前BotC神经元中树突状线粒体的亚细胞变化和细胞色素c氧化酶（CO）活性的组织化学。线粒体电子传递链（ETC）复合物I，IV，V的活动，和膜电位进行分析，在腹外侧髓质含有前BotC区域。我们发现显着减少的平均长度和面积的树突状线粒体在前BotC的CIH大鼠，相比常氧对照组和缺氧组，每天急性间歇性缺氧（dAIH），唤起强大的突触可塑性。值得注意的是，这些形态学改变主要在靠近突触的线粒体中观察到。此外，CIH组中线粒体的比例与扩大的隔间和丝状细胞骨架元素比对照组和dAIH组少。有趣的是，在空间受限的树突棘内的线粒体中观察到了这些结构适应性的独特特征。此外，中度至深色CO反应性线粒体的比例在CIH组中减少，表明线粒体活性降低。CIH组线粒体ETC酶活性和膜电位均降低。这些研究结果表明，缺氧诱导的呼吸可塑性的特点是空间局限的线粒体改变突触后棘在pre-BotC神经元。与dAIH预处理引起的强大可塑性相反，严重的CIH挑战可能会削弱局部线粒体生物能量学，该生物能量学为呼吸马达驱动的突触后活动提供燃料。
Mitochondrial bioenergetics is dynamically coupled with neuronal activities, which are altered by hypoxia-induced respiratory neuroplasticity. Here we report structural features of postsynaptic mitochondria in the pre-Botzinger complex (pre-BotC) of rats treated with chronic intermittent hypoxia (CIH) simulating a severe condition of obstructive sleep apnea. The subcellular changes in dendritic mitochondria and histochemistry of cytochrome c oxidase (CO) activity were examined in pre-BotC neurons localized by immunoreactivity of neurokinin 1 receptors. Assays of mitochondrial electron transport chain (ETC) complex I, IV, V activities, and membrane potential were performed in the ventrolateral medulla containing the pre-BotC region. We found significant decreases in the mean length and area of dendritic mitochondria in the pre-BotC of CIH rats, when compared to the normoxic control and hypoxic group with daily acute intermittent hypoxia (dAIH) that evokes robust synaptic plasticity. Notably, these morphological alterations were mainly observed in the mitochondria in close proximity to the synapses. In addition, the proportion of mitochondria presented with enlarged compartments and filamentous cytoskeletal elements in the CIH group was less than the control and dAIH groups. Intriguingly, these distinct characteristics of structural adaptability were observed in the mitochondria within spatially restricted dendritic spines. Furthermore, the proportion of moderately to darkly CO-reactive mitochondria was reduced in the CIH group, indicating reduced mitochondrial activity. Consistently, mitochondrial ETC enzyme activities and membrane potential were lowered in the CIH group. These findings suggest that hypoxia-induced respiratory plasticity was characterized by spatially confined mitochondrial alterations within postsynaptic spines in the pre-BotC neurons. In contrast to the robust plasticity evoked by dAIH preconditioning, a severe CIH challenge may weaken the local mitochondrial bioenergetics that the fuel postsynaptic activities of the respiratory motor drive.