Popić Jelena, Pešić Vesna, Milanović Desanka, Lončarević-Vasiljković Nataša, Smiljanić Kosara, Kanazir Selma, Ruždijić Sabera
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, 1160 Pine Ave. West, H3A 1A3 Montreal, QC, Canada.
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Int J Dev Neurosci. 2015 Aug;44:22-32. doi: 10.1016/j.ijdevneu.2015.05.003. Epub 2015 May 14.
Propofol anesthesia can trigger pro- and anti-apoptotic signaling pathways in the rat brain. In our previous work, we demonstrated that propofol causes widespread apoptotic neurodegeneration in 7-postnatal-day-old (PND7) but not in PND14 rat neurons. The mechanism responsible for these opposing outcomes is unknown, apparently linked to the specific stage of brain development. The present study aims to elucidate the anti-apoptotic process that is activated in the cortex and thalamus of PND14 Wistar rats during the first 48 h after the onset of propofol anesthesia. We showed that the expression of tumor necrosis factor-α (TNF-α) and several components of its pathway, TNFR1 and caspase-8, was significantly increased in the cortex and thalamus. Nuclear factor kappa B (NF-κB) p65 was downregulated in the cortex and upregulated in the thalamus. The expression of c-Fos was upregulated only in the cortex, showing opposed profile compared to NF-κB p65. Double immunofluorescence staining revealed the colocalization of NF-κB p65 with neuronal marker (NeuN), but with predominantly cytoplasmic localization. Finally, X-linked inhibitor of apoptosis protein (XIAP) was upregulated in both examined structures. Immunohistochemical staining with Iba-1 revealed that the treatment did not induce changes in microglial morphology. Our results (i) reveal that the simultaneous activation of pro- and anti-apoptotic signaling occurs after propofol anesthesia, and (ii) pinpoint the potential neuroprotective role of XIAP in anesthesia-induced neurotoxicity.
丙泊酚麻醉可在大鼠脑内触发促凋亡和抗凋亡信号通路。在我们之前的研究中，我们证明丙泊酚会在出生后7天（PND7）的大鼠神经元中引起广泛的凋亡性神经退行性变，但在PND14的大鼠神经元中则不会。导致这些相反结果的机制尚不清楚，显然与大脑发育的特定阶段有关。本研究旨在阐明在丙泊酚麻醉开始后的头48小时内，PND14 Wistar大鼠的皮质和丘脑中被激活的抗凋亡过程。我们发现，肿瘤坏死因子-α（TNF-α）及其信号通路的几个成分，即TNFR1和半胱天冬酶-8，在皮质和丘脑中的表达显著增加。核因子κB（NF-κB）p65在皮质中下调，在丘脑中上调。c-Fos的表达仅在皮质中上调，与NF-κB p65呈现相反的表达模式。双重免疫荧光染色显示NF-κB p65与神经元标志物（NeuN）共定位，但主要定位于细胞质。最后，X连锁凋亡抑制蛋白（XIAP）在两个检测结构中均上调。用Iba-1进行免疫组织化学染色显示，该处理未诱导小胶质细胞形态的改变。我们的结果（i）表明丙泊酚麻醉后促凋亡和抗凋亡信号同时被激活，（ii）明确了XIAP在麻醉诱导的神经毒性中的潜在神经保护作用。
