Fraley G S, Ritter S
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington 99164-6520, USA.
Endocrinology. 2003 Jan;144(1):75-83. doi: 10.1210/en.2002-220659.
Neuropeptide Y (NPY) and agouti gene-related protein (AGRP) are orexigenic peptides of special importance for control of food intake. In situ hybridization studies have shown that NPY and AGRP mRNAs are increased in the arcuate nucleus of the hypothalamus (ARC) by glucoprivation. Other work has shown that glucoprivation stimulates food intake by activation of hindbrain glucoreceptor cells and requires the participation of rostrally projecting norepinephrine (NE) or epinephrine (E) neurons. Here we determine the role of hindbrain catecholamine afferents in glucoprivation-induced increase in ARC NPY and AGRP gene expression. The selective NE/E immunotoxin saporin-conjugated antidopamine-beta-hydroxylase (anti-dbetah) was microinjected into the medial hypothalamus and expression of AGRP and NPY mRNA was analyzed subsequently in the ARC under basal and glucoprivic conditions using (33)P-labeled in situ hybridization. Saporin-conjugated anti-dbetah virtually eliminated dbetah-immunoreactive terminals in the ARC without causing nonspecific damage. These lesions significantly increased basal but eliminated 2-deoxy-D-glucose-induced increases in AGRP and NPY mRNA expression. Results indicate that hindbrain catecholaminergic neurons contribute to basal NPY and AGRP gene expression and mediate the responsiveness of NPY and AGRP neurons to glucose deficit. Our results also suggest that catecholamine neurons couple potent orexigenic neural circuitry within the hypothalamus with hindbrain glucose sensors that monitor brain glucose supply.
神经肽Y（NPY）和刺鼠基因相关蛋白（AGRP）是对食物摄入控制具有特殊重要性的促食欲肽。原位杂交研究表明，通过糖剥夺，下丘脑弓状核（ARC）中的NPY和AGRP mRNA会增加。其他研究表明，糖剥夺通过激活后脑葡萄糖受体细胞来刺激食物摄入，并且需要向前投射的去甲肾上腺素（NE）或肾上腺素（E）神经元的参与。在这里，我们确定后脑儿茶酚胺传入神经在糖剥夺诱导的ARC中NPY和AGRP基因表达增加中的作用。将选择性NE/E免疫毒素皂草素偶联的抗多巴胺-β-羟化酶（抗-dbetah）显微注射到下丘脑内侧，随后在基础和糖剥夺条件下，使用（33）P标记的原位杂交技术分析ARC中AGRP和NPY mRNA的表达。皂草素偶联的抗-dbetah几乎消除了ARC中dbetah免疫反应性终末，而不会造成非特异性损伤。这些损伤显著增加了基础状态下的AGRP和NPY mRNA表达，但消除了2-脱氧-D-葡萄糖诱导的增加。结果表明，后脑儿茶酚胺能神经元有助于基础状态下的NPY和AGRP基因表达，并介导NPY和AGRP神经元对葡萄糖缺乏的反应性。我们的结果还表明，儿茶酚胺神经元将下丘脑内强大的促食欲神经回路与监测脑葡萄糖供应的后脑葡萄糖传感器联系起来。
