Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan; Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
Peptides. 2020 Jul;129:170313. doi: 10.1016/j.peptides.2020.170313. Epub 2020 Apr 13.
Experimental allergic encephalomyelitis (EAE) is considered to be a useful animal model of human multiple sclerosis (MS). However, among the various symptoms of MS, the mechanisms contributing to inflammatory anorexia remain unclear. In the present study, we used an EAE rat model to examine changes in expression levels of hypothalamic feeding-related peptide genes and neuroendocrine responses such as the hypothalamo-neurohypophysial system and the hypothalamo-pituitary-adrenal (HPA) axis. The weight gain and cumulative food intake in EAE rats in the early days after immunization was significantly lower than that of the control group. The expression of orexigenic peptide genes Npy and Agrp were significantly increased, whereas the levels of anorectic peptide genes (Pomc and Cart) were significantly decreased in the hypothalamus of EAE rats. There was also a significant increase in the mRNA and plasma oxytocin (OXT) but not of arginine vasopressin (AVP) in the supraoptic and paraventricular nuclei (PVN) of EAE rats at days 12 and 18 after immunization. The expression of corticotropin-releasing hormone (Crh) and Avp was downregulated and upregulated, respectively, in the parvocellular division of the PVN at day 12 after immunization. The expression level of Pomc in the anterior pituitary significantly increased, accompanied by increased plasma corticosterone levels, at days 6, 12, and 18 after immunization. These results suggest that inflammatory anorexia in rat EAE may be caused by activation of the OXT-ergic pathway and HPA axis via changes in the expression of hypothalamic feeding-related peptides, including Avp but not Crh.
实验性自身免疫性脑脊髓炎（EAE）被认为是人类多发性硬化症（MS）的有用动物模型。然而，在 MS 的各种症状中，导致炎症性厌食的机制仍不清楚。在本研究中，我们使用 EAE 大鼠模型来研究下丘脑摄食相关肽基因的表达水平变化以及神经内分泌反应，如下丘脑-神经垂体系统和下丘脑-垂体-肾上腺（HPA）轴。免疫后早期 EAE 大鼠的体重增加和累计食物摄入量明显低于对照组。EAE 大鼠下丘脑食欲肽基因（Npy 和 Agrp）的表达显著增加，而厌食肽基因（Pomc 和 Cart）的水平显著降低。在免疫后 12 天和 18 天，EAE 大鼠的视上核和室旁核（PVN）中催产素（OXT）的 mRNA 和血浆水平显著增加，但精氨酸加压素（AVP）没有增加。在免疫后 12 天，PVN 的小细胞区中促皮质素释放激素（Crh）和 Avp 的表达分别下调和上调。免疫后 6、12 和 18 天，垂体前叶 Pomc 的表达水平显著增加，同时血浆皮质酮水平升高。这些结果表明，EAE 大鼠的炎症性厌食可能是由于下丘脑摄食相关肽（包括 Avp 但不包括 Crh）表达的变化，激活了 OXT 能途径和 HPA 轴。
