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Crucial involvement of catecholamine neurotransmission in postoperative nausea and vomiting: Whole-transcriptome profiling in the rat nucleus of the solitary tract
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2021-06-10 , DOI: 10.1111/gbb.12759
Shigekazu Sugino 1 , Daisuke Konno 1 , Junko Abe 1 , Yuka Imamura-Kawasawa 2 , Kanta Kido 3 , Jun Suzuki 1 , Yasuhiro Endo 1 , Masanori Yamauchi 1
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The genetic mechanisms of postoperative nausea and vomiting (PONV) and the involvement of the catecholamine system in the brain have not been elucidated. Eating kaolin clay as a type of pica has been examined as an alternative behavior to emesis. Here, we evaluated changes in whole-transcriptome analysis in the nucleus of the solitary tract (NTS) in a rat pica model as a surrogate behavior of PONV to elucidate the molecular genetic mechanisms of the development of PONV and the involvement of the catecholamine system in the NTS. First, kaolin pica behaviors were investigated in 71 female Wistar rats following isoflurane anesthesia, surgical insult or morphine administration. Multiple linear regression analysis showed that 3 mg/kg morphine increased kaolin intake by 2.8 g (P = 0.0002). Next, total RNA and protein were extracted from the dissected NTS, and whole-transcriptome sequencing (RNA-seq) was performed to identify PONV-associated genes and to verify the involvement of the catecholamine system. The gene expression levels of tyrosine hydroxylase and dopamine beta-hydroxylase in the catecholamine biosynthesis pathway decreased significantly in the PONV model. Release of noradrenaline, a catecholamine pathway end product, may have increased at the synaptic terminal of the NTS neuron after pica behavior. Systematic administration of α2 adrenergic receptor agonists after surgery reduced kaolin intake from 3.2 g (control) to 1.0 g (P = 0.0014). These results indicated that catecholamine neurotransmission was involved in the development of PONV in the NTS.

中文翻译:


儿茶酚胺神经传递在术后恶心和呕吐中的关键作用:大鼠孤束核的全转录组分析



术后恶心呕吐(PONV)的遗传机制以及大脑中儿茶酚胺系统的参与尚未阐明。吃高岭土作为异食癖的一种,已被视为呕吐的替代行为。在这里,我们评估了大鼠异食癖模型中孤束核(NTS)的全转录组分析变化,作为 PONV 的替代行为,以阐明 PONV 发生的分子遗传机制以及儿茶酚胺系统参与NTS。首先,对 71 只雌性 Wistar 大鼠在异氟烷麻醉、手术损伤或吗啡给药后的高岭土异食癖行为进行了研究。多元线性回归分析显示,3 mg/kg 吗啡使高岭土摄入量增加 2.8 g( P = 0.0002)。接下来,从解剖的 NTS 中提取总 RNA 和蛋白质,并进行全转录组测序 (RNA-seq) 以鉴定 PONV 相关基因并验证儿茶酚胺系统的参与。 PONV模型中儿茶酚胺生物合成途径中酪氨酸羟化酶和多巴胺β-羟化酶的基因表达水平显着下降。异食癖行为后,NTS 神经元突触末端的去甲肾上腺素(一种儿茶酚胺途径终产物)的释放可能增加。手术后系统给予α2肾上腺素受体激动剂将高岭土摄入量从3.2克(对照)减少到1.0克( P = 0.0014)。这些结果表明儿茶酚胺神经传递参与了 NTS 中 PONV 的发生。
更新日期:2021-07-07
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