Lung-injury depresses glutamatergic synaptic transmission in the nucleus tractus solitarii via discrete age-dependent mechanisms in neonatal rats.
Lung-injury depresses glutamatergic synaptic transmission in the nucleus tractus solitarii via discrete age-dependent mechanisms in neonatal rats.
复制标题
DOI：
10.1016/j.bbi.2018.03.031
复制
发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Jacono FJ
中科院分区：
文献类型：
--
作者：
Litvin DG;Dick TE;Smith CB;Jacono FJ
过渡期（tp）是中枢神经系统发育的短暂阶段，在此期间神经回路对损伤或感染等病理条件表现出高度脆弱性。这种易感性部分是由于突触可塑性的特殊机制，它可能在病理条件下被释放的炎症介质激活。因此，我们假设肺损伤（LI）的免疫反应通过可塑性样机制介导突触变化，这取决于LI是发生在TP之前还是之后。我们研究了LI在出生后第11 - 15天的呼吸控制TP期间对位于孤束核（nTS）的脑干二级脏器感觉神经元的影响。我们在TP之前（P9 - 11）或之后（P17 - 19）气管内灌注博莱霉素（或生理盐水）损伤Sprague-Dawley大鼠的肺。一周后，我们准备了髓质水平切片，并记录了nTS神经元在体外接受来自孤独束（TS）的单突触谷氨酸能输入的自发和诱发兴奋性突触后电流（sEPSCs/eEPSCs）。在TP前损伤的大鼠中，与对照组相比，神经元表现出钝化的sEPSCs和TS-eEPSCs。突触后α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的差异介导了TS-eEPSCs的减少。具体来说，与对照组相比，LI大鼠具有更多的Ca2+不透性AMPARs (CI-AMPARs)，这表明：1)没有电流矫正，2)对多胺，1-萘酰乙酰精胺-三盐酸（NASPM）的敏感性降低，3)CI-AMPAR GluA2的免疫反应性染色增强。因此，前tp - li在突触后起钝化谷氨酸传递的作用。对前tp - li的神经免疫反应包括整个nTS的小胶质细胞超分支。每天腹腔注射米诺环素（一种小胶质细胞/巨噬细胞功能抑制剂）可防止超分支化，并消除tp - li前引起的突触变化。相比之下，与对照组相比，TP后损伤的大鼠幼崽在nTS中表现出小胶质细胞低分支，sEPSC振幅/频率增加，TS-eEPSC振幅降低。这些突触变化与ci - ampar的变化无关，而是涉及更大的ts诱发的使用依赖性抑制（配对脉冲比降低），这是突触前可塑性的标志。因此，我们得出结论，LI通过免疫介导的离散可塑性样机制调节TS《nTS》突触的疗效，并取决于损伤是发生在TP呼吸控制之前还是之后。
Transition periods (TPs) are brief stages in CNS development where neural circuits can exhibit heightened vulnerability to pathologic conditions such as injury or infection. This susceptibility is due in part to specialized mechanisms of synaptic plasticity, which may become activated by inflammatory mediators released under pathologic conditions. Thus, we hypothesized that the immune response to lung injury (LI) mediated synaptic changes through plasticity-like mechanisms that depended on whether LI occurred just before or after a TP. We studied the impact of LI on brainstem 2nd-order viscerosensory neurons located in the nucleus tractus solitarii (nTS) during a TP for respiratory control spanning (postnatal day (P) 11 – 15). We injured the lungs of Sprague-Dawley rats by intratracheal instillation of Bleomycin (or saline) just before (P9 – 11) or after (P17 – 19) the TP. A week later, we prepared horizontal slices of the medulla and recorded spontaneous and evoked excitatory postsynaptic currents (sEPSCs/eEPSCs) in vitro from neurons in the nTS that received monosynaptic glutamatergic input from the tractus solitarii (TS). In rats injured before the TP (pre-TP), neurons exhibited blunted sEPSCs and TS-eEPSCs compared to controls. The decreased TS-eEPSCs were mediated by differences in postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid receptors (AMPAR). Specifically, compared to controls, LI rats had more Ca2+-impermeable AMPARs (CI-AMPARs) as indicated by: 1) the absence of current-rectification, 2) decreased sensitivity to polyamine, 1-Naphthyl-acetyl-spermine-trihydrochloride (NASPM) and 3) augmented immunoreactive staining for the CI-AMPAR GluA2. Thus, pre-TP-LI acts postsynaptically to blunt glutamatergic transmission. The neuroimmune response to pre-TP-LI included microglia hyper-ramification throughout the nTS. Daily intraperitoneal administration of minocycline, an inhibitor of microglial/macrophage function prevented hyper-ramification and abolished the pre-TP-LI evoked synaptic changes. In contrast, rat-pups injured after the TP (post-TP) exhibited microglia hypo-ramification in the nTS and had increased sEPSC amplitudes/frequencies, and decreased TS-eEPSC amplitudes compared to controls. These synaptic changes were not associated with changes in CI-AMPARs, and instead involved greater TS-evoked use-dependent depression (reduced paired pulse ratio), which is a hallmark of presynaptic plasticity. Thus we conclude that LI regulates the efficacy of TS➔nTS synapses through discrete plasticity-like mechanisms that are immune-mediated and depend on whether the injury occurs before or after the TP for respiratory control.
登录
查看更多内容
影响因子：
4.4
作者：
Babin, Anna L.;Cannet, Catherine;Beckmann, Nicolau
通讯作者：
Beckmann, Nicolau
DOI：
10.1073/pnas.91.22.10380
发表时间：
1994-10-25
影响因子：
11.1
作者：
ALLEN, C;STEVENS, CF
通讯作者：
STEVENS, CF
影响因子：
5.3
作者：
Chater TE;Goda Y
通讯作者：
Goda Y
影响因子：
5.3
作者：
Brill, Julia;Huguenard, John R.
通讯作者：
Huguenard, John R.
影响因子：
5.3
作者：
Clark, Anna K.;Gruber-Schoffnegger, Doris;Sandkuehler, Juergen
通讯作者：
Sandkuehler, Juergen