Alterations in synapses and mitochondria induced by acute or chronic intermittent hypoxia in the pre-Bötzinger complex of rats: an ultrastructural triple-labeling study with immunocytochemistry and histochemistry.

Alterations in synapses and mitochondria induced by acute or chronic intermittent hypoxia in the pre-Bötzinger complex of rats: an ultrastructural triple-labeling study with immunocytochemistry and histochemistry.
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DOI:
10.3389/fncel.2023.1132241
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发表时间:
2023
影响因子:
5.3
通讯作者:
--
中科院分区:
医学2区
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前BötC复合体(pre-BötC)是吸气节律发生的核心,是由兴奋性谷氨酸能和抑制性GABA能和甘氨酸能神经元组成的异质网络。吸气节律的产生依赖于兴奋性神经元的同步激活,而抑制性神经元在塑造呼吸模式方面发挥关键作用,赋予节律适应环境,代谢和行为需求的灵活性。在这里,我们报告的超微结构的变化,兴奋性,不对称突触(AS)和抑制性,对称突触(SS),特别是穿孔突触与不连续的突触后密度(PSD)在前BötC大鼠暴露于每日急性间歇性缺氧(dAIH)或慢性(C)IH。我们首次利用生长抑素(SST)和神经激肽1受体(NK 1 R)双重免疫细胞化学与细胞色素氧化酶组织化学相结合,揭示了前BötC的突触特征和线粒体动力学。我们发现穿孔突触与突触囊泡积累在不同的池并列每个离散PSD段。dAIH诱导黄斑AS的PSD大小和穿孔突触的比例显著增加。dAIH组以AS为主,CIH组以SS为主。dAIH显著增加SST和NK 1 R的表达,而CIH导致SST和NK 1 R的表达下降。桥粒样接触(DLC)的特点是第一次在前BötC。它们分布于突触旁,尤其是SS。线粒体出现在更接近DLC比突触,提示更高的能量需求的DLC。单棘双AS和SS神经支配的结果提供了形态学证据的兴奋-抑制的相互作用在一个单一的脊柱在pre-BötC。特别是,我们的特点是集中的突触与线粒体定位,可以作为一个结构基础的同步性的脊柱轴通信的脊柱轴微区。在棘内发现了线粒体,并在前BötC中首次描绘了线粒体融合和分裂的超微结构特征。我们提供了轴和棘中兴奋抑制突触的超微结构证据,以及与突触相关的DLC,这些突触与线粒体动力学在前BötC中对呼吸可塑性的贡献一致。
The pre-Bötzinger complex (pre-BötC), a kernel of inspiratory rhythmogenesis, is a heterogeneous network with excitatory glutamatergic and inhibitory GABAergic and glycinergic neurons. Inspiratory rhythm generation relies on synchronous activation of glutamatergic neuron, whilst inhibitory neurons play a critical role in shaping the breathing pattern, endowing the rhythm with flexibility in adapting to environmental, metabolic, and behavioral needs. Here we report ultrastructural alterations in excitatory, asymmetric synapses (AS) and inhibitory, symmetric synapses (SS), especially perforated synapses with discontinuous postsynaptic densities (PSDs) in the pre-BötC in rats exposed to daily acute intermittent hypoxia (dAIH) or chronic (C) IH. We utilized for the first time a combination of somatostatin (SST) and neurokinin 1 receptor (NK1R) double immunocytochemistry with cytochrome oxidase histochemistry, to reveal synaptic characteristics and mitochondrial dynamic in the pre-BötC. We found perforated synapses with synaptic vesicles accumulated in distinct pools in apposition to each discrete PSD segments. dAIH induced significant increases in the PSD size of macular AS, and the proportion of perforated synapses. AS were predominant in the dAIH group, whereas SS were in a high proportion in the CIH group. dAIH significantly increased SST and NK1R expressions, whereas CIH led to a decrease. Desmosome-like contacts (DLC) were characterized for the first time in the pre-BötC. They were distributed alongside of synapses, especially SS. Mitochondria appeared in more proximity to DLC than synapses, suggestive of a higher energy demand of the DLC. Findings of single spines with dual AS and SS innervation provide morphological evidence of excitation-inhibition interplay within a single spine in the pre-BötC. In particular, we characterized spine-shaft microdomains of concentrated synapses coupled with mitochondrial positioning that could serve as a structural basis for synchrony of spine-shaft communication. Mitochondria were found within spines and ultrastructural features of mitochondrial fusion and fission were depicted for the first time in the pre-BötC. We provide ultrastructural evidence of excitation-inhibition synapses in shafts and spines, and DLC in association with synapses that coincide with mitochondrial dynamic in their contribution to respiratory plasticity in the pre-BötC.
树突状GABA能抑制的输入特异性NMDAR依赖性增强。
DOI: 10.1016/j.neuron.2017.12.032
发表时间: 2018-01-17
期刊: Neuron
影响因子: 16.2
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发表时间: 2016-08-01
期刊: HYPERTENSION
影响因子: 8.3
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发表时间: 1987-10-13
期刊: BRAIN RESEARCH
影响因子: 2.9
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通讯作者: DETOLEDOMORRELL, L