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

本研究旨在从遗传学、分子生物学、形态学和生理学等方面探讨心血管相关肽在中枢神经系统（CNS）中的作用。这些方法侧重于从遗传学到心血管相关肽在中枢神经系统中的行为的综合研究。检测的心血管相关肽有抗利尿激素、肾上腺髓质素、食欲素/下丘脑泌素、瘦素、TRH、CRH、尿皮质素和PACAP。(1)遗传性多饮小鼠下丘脑抗利尿激素基因表达上调。(2)肾上腺髓质样免疫反应细胞分布于下丘脑区，包括室旁核（PVN）和视上核（SON）。肾上腺髓质素中央给药选择性激活PVN和SON中的催产素分泌神经元，血浆催产素升高。(3)食欲素/下丘脑分泌素是新发现的促氧肽。更多的诱导神经元位于下丘脑外侧区。它们的轴突投射到中枢神经系统的各个区域。中央给药食欲素选择性激活大鼠下丘脑-垂体-肾上腺轴。观察大鼠新生期食欲素的发育情况。在出生后15天和20天，促食素基因的表达明显增加。(4)用瘦素替代可防止食物剥夺引起的PVN神经元一氧化氮合酶基因、TRH基因和CRH基因下调。(5)高血压盐敏感大鼠SON中尿尿素生成细胞和纤维的免疫反应性升高。(6)中央给药PACAP激活PVN和SON的抗利尿激素分泌细胞，引起PVN和SON中抗利尿激素异核RNA的增加。Kainic酸诱导癫痫发作可显著诱导大鼠PVN细小细胞分裂中PACAP基因的表达。此外，研究心血管相关肽在中枢神经系统中的作用也很重要。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