Role of Cardiovascular-related Peptides in the Brain : Genetic, Molecular Biological, Morphological and Physiological Aspects.

本研究的目的是利用遗传学、分子生物学、形态学和生理学的方法，研究心血管相关肽在中枢神经系统中的作用。这些方法侧重于从遗传学到行为在中枢神经系统心血管相关多肽的作用的综合研究。被检测的心血管相关多肽为血管加压素、肾上腺髓质素、增食欲素/下丘脑皮质激素、瘦素、促肾上腺皮质激素释放激素、促肾上腺皮质激素释放激素、尿皮质素和PACAP。(1)遗传性糖尿病小鼠下丘脑血管加压素基因表达上调。(2)肾上腺髓质素样免疫反应细胞分布于大鼠下丘脑区，包括室旁核(PVN)和视上核(SON)。中枢注射肾上腺髓质素可选择性地激活PVN和SON内分泌催产素的神经元，并伴有血浆催产素的升高。(3)食欲素/下克汀肽是新发现的食欲肽。食欲素-Pr…下丘脑外侧区有较多的产生型神经元。它们的轴突投射到中枢神经系统的不同区域。中枢注射增食欲素选择性激活大鼠下丘脑-垂体肾上腺轴。观察新生大鼠食欲素的发育情况。在出生后15天和20天，食欲素基因的表达显著增加。(4)瘦素可预防食物剥夺引起的下丘脑室旁核神经元型一氧化氮合酶基因、TRH基因和CRH基因表达下调。(5)高血压性盐敏感Dahl大鼠SON内Urocotin产生细胞和纤维的免疫反应增强。(6)中枢注射PACAP激活了PVN和SON中的加压素分泌细胞，使PVN和SON中的加压素异核RNA增加。海人酸致痫大鼠下丘脑室旁核小细胞分裂中PACAP基因明显诱导。此外，重要的是要研究心血管相关肽在中枢神经系统中的作用。较少

The purpose of the present study was to investigate the role of cardiovascular-related peptides in the central nervous system (CNS), using genetic, molecular biological, morphological and physiological approaches. These approaches focused on the integrative investigation of the role from the genetics to behavior of cardiovascular-related peptides in the CNS. The examined cardiovascular-related peptides were vasopressin, adrenomedullin, orexin/hypocretin, leptin, TRH, CRH, urocortin and PACAP. (1) The expression of the vasopressin gene in the hypothalamus was upregulated in genetically polydipsic mice. (2) Adrenomedullin-like immunoreactive cells were distributed in the hypothalamic area, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of rats. Central administration of adrenomedullin selectively activated oxytocin-secreting neurons in the PVN and the SON with elevation of plasma oxytocin. (3) Orexin/hypocretin was newly discovered orexigenic peptides. Orexin-pr … More oducing neurons were localized in the lateral hypothalamic area. Their axons project to various regions in the CNS. Central administration of orexin selectively activated hypothalamo-pituitary adrenal axis in rats. Neonatal development of orexin in rats were examined. The expression of the orexin gene was markedly increased 15 and 20 days after birth. (4) The food deprivation induced down-regulation of neuronal nitric oxide synthase gene, TRH gene and CRH gene in the PVN were prevented by replacement with leptin. (5) The immunoreactivity of urocotin-producing cells and fibers in the SON was increased in the SON of hypertensive salt sensitive Dahl rats. (6) Central administration of PACAP activated vasopressin-secreting cells in the PVN and the SON and caused an increase in vasopressin heteronuclear RNA in the PVN and the SON. Kainic acid-induced seizure caused a marked induction of the PACAP gene in the parvocellular division of the PVN of rats. Furthermore, it is important to examine the role of cardiovascular-related peptides in the CNS. Less