Daily acute intermittent hypoxia induced dynamic changes in dendritic mitochondrial ultrastructure and cytochrome oxidase activity in the pre-Botzinger complex of rats
Daily acute intermittent hypoxia induced dynamic changes in dendritic mitochondrial ultrastructure and cytochrome oxidase activity in the pre-Botzinger complex of rats
复制标题
每日急性间歇性缺氧诱导大鼠前Bötzinger复合体树突状线粒体超微结构和细胞色素氧化酶活性的动态变化
DOI：
10.1016/j.expneurol.2018.12.008
复制
发表时间：
2019-03-01
影响因子：
5.3
通讯作者：
Liu, Ying-Ying
中科院分区：
文献类型：
--
作者：
Kang, Jun-Jun;Guo, Baolin;Liu, Ying-Ying
线粒体作为初级能量发生器和Ca 2+生物传感器，与神经元活动动态耦合，从而在神经可塑性中发挥作用。在这里，我们报告，呼吸神经可塑性引起的每日急性间歇性缺氧（dAIH）诱发适应性变化的超微结构和突触后分布的线粒体在前Botzinger复杂（前BotC）。在用dAIH预处理的成年Sprague-Dawley大鼠的前BotC神经元中检查神经元活性的代谢标志物、细胞色素c氧化酶（CO）和树突状线粒体，已知dAIH诱导呼吸神经活动的长时程易化（LTF）。我们进行神经激肽1受体（NK 1 R）预包埋免疫细胞化学，以确定前BotC神经元，结合CO组织化学，描绘树突状线粒体的超微结构改变和CO活性。我们发现dAIH攻击显著增加了前BotC神经元中的CO活性。dAIH组突触后部位的一氧化碳反应性线粒体比常氧对照组更为普遍。此外，线粒体的长度和面积显着增加，在dAIH组，这意味着更大的表面积的嵴ATP的产生。有一个很好的，结构重塑，显着扩大和分支线粒体或锥形线粒体延伸到树突棘。线粒体嵴以平行层状排列为主，能量产生效率高。此外，在线粒体和突触后膜之间还观察到絮状或类似絮状的成分。这些形态学证据，加上增加的CO活性，表明树突状线粒体在前BotC动态响应呼吸可塑性。因此，可塑性神经元的变化与活跃的线粒体生物能量学密切相关，导致能量产生和Ca 2+缓冲增强，这可能驱动LTF表达。
Mitochondria, as primary energy generators and Ca2+ biosensor, are dynamically coupled to neuronal activities, and thus play a role in neuroplasticity. Here we report that respiratory neuroplasticity induced by daily acute intermittent hypoxia (dAIH) evoked adaptive changes in the ultrastructure and postsynaptic distribution of mitochondria in the pre-Botzinger complex (pre-BotC). The metabolic marker of neuronal activity, cytochrome c oxidase (CO), and dendritic mitochondria were examined in pre-BotC neurons of adult Sprague-Dawley rats preconditioned with dAIH, which is known to induce long-term facilitation (LTF) in respiratory neural activities. We performed neurokinin 1 receptor (NK1R) pre-embedding immunocytochemistry to define pre-BotC neurons, in combination with CO histochemistry, to depict ultrastructural alterations and CO activity in dendritic mitochondria. We found that the dAIH challenge significantly increased CO activity in pre-BotC neurons. Darkly CO-reactive mitochondria at postsynaptic sites in the dAIH group were much more prevalent than those in the normoxic control. In addition, the length and area of mitochondria were significantly increased in the dAIH group, implying a larger surface area of cristae for ATP generation. There was a fine, structural remodeling, notably enlarged and branching mitochondria or tapered mitochondria extending into dendritic spines. Mitochondria] cristae were mainly in parallel-lamellar arrangement, indicating a high efficiency of energy generation. Moreover, flocculent or filament-like elements were noted between the mitochondria and the postsynaptic membrane. These morphological evidences, together with increased CO activity, demonstrate that dendritic mitochondria in the pre-BotC responded dynamically to respiratory plasticity. Hence, plastic neuronal changes are closely coupled to active mitochondrial bioenergetics, leading to enhanced energy production and Ca2+ buffering that may drive the LTF expression.