Novel feeding-related peptides and stress reaction -Molecular based study and physiological investigation-

本项目的目的是研究新的摄食相关多肽可能通过中枢神经系统参与应激诱导的生理反应，如自主神经和内分泌反应。在本项目中，食欲素/下克汀类、神经中性素U和甘丙肽样肽(GALP)被集中在与摄食相关的新多肽上。(1)限食、缺糖、限制应激和冷应激可激活大鼠下丘脑外侧区产生食欲素的神经元。中枢注射增食欲素-A激活室旁核(PVN)和杏仁中央核(CPN)内CRH产生神经元。(2)中枢神经递质U兴奋大鼠下丘脑室旁核神经元，刺激ACTH、加压素和催产素的分泌。(3)渗透压刺激、内毒素休克和慢性炎症应激可上调大鼠垂体前叶GALP基因的表达。内毒素休克大鼠弓状核GALP基因表达显着升高。遗传性肥胖大鼠(FA/FA)弓状核GALP基因表达水平显著低于对照组(Fa/？)，而垂体前叶GALP基因表达水平高于对照组(Fa/？)。

The purpose of this project is to investigate the possible involvement of novel feeding-related peptides in the stress-induced physiological reactions via central nervous system such as autonomic nervous and endocrine responses. Orexins/hypocretins, neuromedin U and galanin-like peptide (GALP) were focused on the novel feeding-related peptides in the present project. (1)Feeding restriction, glucodeprivation, restrict stress and cold stress caused activation of orexin-producing neurons in the lateral hypothalamic area of rats. Centrally administered orexin-A activated CRH-producing neurons in the paraventricular nucleus (PVN) and the central amygdaloid nucleus of rats. (2)Central administration of neuromedin U activated neurons in the rat PVN and stimulated the secretions of ACTH, vasopressin and oxytocin. (3)The expression of the GALP gene in the rat anterior pituitary gland was upregulated by osmotic challenge, lipopolysaccharide (LPS)-induced endotoxin shock and chronic inflammatory stress. In the rat arcuate nucleus GALP mRNA level was significantly increased during endotoxin shock. In genetically obese rats (fa/fa) GALP mRNA level in the arcuate nucleus was significantly lower than that in control (Fa/?), while GALP mRNA in the anterior pituitary was higher than that in control (Fa/?).