CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles & Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Peptides. 2010 Feb;31(2):263-70. doi: 10.1016/j.peptides.2009.11.015. Epub 2009 Nov 26.
Abdominal surgery-induced postoperative gastric ileus is well established to induce Fos expression in specific brain nuclei in rats within 2-h after surgery. However, the phenotype of activated neurons has not been thoroughly characterized. Nesfatin-1 was recently discovered in the rat hypothalamus as a new anorexigenic peptide that also inhibits gastric emptying and is widely distributed in rat brain autonomic nuclei suggesting an involvement in stress responses. Therefore, we investigated whether abdominal surgery activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Two hours after abdominal surgery with cecal palpation under short isoflurane anesthesia or anesthesia alone, rats were transcardially perfused and brains processed for double immunohistochemical labeling of Fos and nesfatin-1. Abdominal surgery, compared to anesthesia alone, induced Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), Edinger-Westphal nucleus (EW), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling showed that of the activated cells, 99% were nesfatin-1-immunoreactive in the SON, 91% in the LC, 82% in the rRPa, 74% in the EW and VLM, 71% in the anterior parvicellular PVN, 47% in the lateral magnocellular PVN, 41% in the medial magnocellular PVN, 14% in the NTS and 9% in the medial parvicellular PVN. These data established nesfatin-1 immunoreactive neurons in specific nuclei of the hypothalamus and brainstem as part of the neuronal response to abdominal surgery and suggest a possible implication of nesfatin-1 in the alterations of food intake and gastric transit associated with such a stressor.
腹部手术引起的术后胃轻瘫已被证实可在手术后 2 小时内诱导大鼠特定脑核内 Fos 表达。然而,激活神经元的表型尚未得到彻底描述。Nesfatin-1 最近在大鼠下丘脑被发现是一种新的厌食肽,它也抑制胃排空,广泛分布于大鼠脑自主神经核,提示其参与应激反应。因此,我们研究了腹部手术是否会激活大鼠脑内的 nesfatin-1 免疫反应性(ir)神经元。在短异氟烷麻醉下或单独麻醉下进行腹部手术(触诊盲肠)后 2 小时,通过心脏灌注后灌注并对 Fos 和 nesfatin-1 进行双重免疫组织化学标记。与单独麻醉相比,腹部手术可诱导视上核(SON)、室旁核(PVN)、蓝斑核(LC)、脑桥头端被盖核(EW)、中缝背核(rRPa)、孤束核(NTS)和腹外侧延髓(VLM)神经元中的 Fos 表达。双 Fos/nesfatin-1 标记显示,在激活的细胞中,99%在 SON 中是 nesfatin-1 免疫反应性的,91%在 LC 中,82%在 rRPa 中,74%在 EW 和 VLM 中,71%在前小细胞 PVN 中,47%在外侧大细胞 PVN 中,41%在中间大细胞 PVN 中,14%在 NTS 中,9%在中间小细胞 PVN 中。这些数据确立了 nesfatin-1 免疫反应性神经元是下丘脑和脑干特定核的一部分,是对腹部手术的神经元反应的一部分,并提示 nesfatin-1 可能参与与这种应激相关的食物摄入和胃转运的改变。