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

新型喂养相关肽和应激反应-基于分子的研究和生理学研究-

• 批准号: 14370026
• 负责人: UETA Yoichi
• 金额: $ 8.9万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370026/
• 关键词: Stress reaction; Central regulation of feeding; Hypothalamus; CRH; orexin; neuromedin U; galanin-like peptide; Fos; 視床下部-下垂体-副腎軸; 下垂体後葉系; アドレノメデユリン; CRF

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/?).

本研究的目的是探讨新型摄食相关肽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。本课题重点研究了食欲素/下丘脑分泌素、神经介肽U和甘丙肽类肽（Galanin-like peptide，GALP）。（1）限食、缺糖、限制应激和冷应激均可引起大鼠下丘脑外侧区食欲素神经元的激活。中枢给药食欲素-A激活大鼠室旁核（PVN）和中央杏仁核中的CRH产生神经元。（2）中枢注射neumedinU可激活大鼠PVN神经元，促进ACTH、加压素和催产素的分泌。（3）渗透压刺激、脂多糖（LPS）诱导的内毒素休克和慢性炎症应激均可上调大鼠垂体前叶GALP基因的表达。在大鼠弓状核GALP mRNA水平显着增加在内毒素休克。在遗传性肥胖大鼠（fa/fa）中，弓状核中的GALP mRNA水平显著低于对照组（Fa/？），垂体前叶GALP mRNA表达高于对照组（Fa/？）。

项目成果

芹野 良太 et al.: "血管"日本心脈管作動物質学会. 165-169 (2002)

Ryota Serino 等人：“Vasles”日本心血管药物学会 165-169 (2002)。

Yamamoto, Y., Ueta, Y., Yamashita, H., Asayama K., Shirahata, A.: "Expression of the prepro-orexin and orexin type 2 receptor genes in obese rat."Peptides. 23(9). 1689-1696 (2002)

Yamamoto, Y.、Ueta, Y.、Yamashita, H.、Asayama K.、Shirahata, A.：“肥胖大鼠中前食欲素原和食欲素 2 型受体基因的表达。”肽。

Shibuya, I.et al.: "Regulation of catecholamine synthesis by leptin"Annual NY Academy of Science. 971. 522-527 (2002)

Shibuya, I.等人：“瘦素对儿茶酚胺合成的调节”纽约科学院年刊。

Nomura, M., Serino, R., Yamamoto, Y., Ozaki, Y., Saito, J., Matsumoto, T., Yamashita, H., Ueta, Y.: "Upregulation of the CRH gene expression and downregulation of the arginine vasopressin gene expression in the hypothalamus of bilateral nephrectomized rat

Nomura, M.、Serino, R.、Yamamoto, Y.、Ozaki, Y.、Saito, J.、Matsumoto, T.、Yamashita, H.、Ueta, Y.：“CRH 基因表达的上调和 CRH 基因表达的下调

Saito, J., Ozaki, Y., Ohnishi, H., Nakamura, T., Ueta, Y.: "Induction of galanin-like peptide gene expression in the rat posterior pituitary gland during endotoxin shock and adjuvant arthritis."Molecular Brain Research. 113. 124-132 (2003)

Saito, J.、Ozaki, Y.、Ohnishi, H.、Nakamura, T.、Ueta, Y.：“内毒素休克和佐剂性关节炎期间大鼠垂体后叶中甘丙肽样肽基因表达的诱导。”分子脑