Briski K P, Sylvester P W
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana Monroe, 71209, USA.
Neuroreport. 2001 Mar 5;12(3):531-4. doi: 10.1097/00001756-200103050-00020.
Reports that glucose antimetabolite treatment elicits hyperphagia and hyperglycemia suggest that decreased oxidation of this energy substrate elicits compensatory responses that enhance cellular fuel availability. Neurons the lateral hypothalamic area (LHA) synthesize the orectic neuropeptide, orexin-A (ORX-A). The present study evaluated the functional responsiveness of orexinergic neurons to glucopenia by investigating whether these cells express the genomic regulatory protein, Fos, in response to glucoprivation. Adult male rats were sacrificed 2h after i.p. (400 mg/kg) or intracerebroventricular (i.c.v.; 100 microg) administration of the antimetabolite, 2-deoxy-D-glucose (2DG) or saline. Sections through the LHA, from the level of the paraventricular nucleus (PVN) to the posterior hypothalamic area (PHA), were processed by dual-label immunocytochemistry for Fos- and OXY-A-immunoreactivity (-ir). Although orexinergic neurons expressed negligible Fos-ir following vehicle administration, dual-labeled ORX-A neurons were observed in the LHA, as well as the dorsomedial hypothalamic nucleus (DMN) and PHA, in both drug-treated groups. Bilateral cell counts from representative levels of the LHA, DMN, and PHA showed that in each structure, a greater proportion of ORX-A neurons were immunostained for Fos in response to systemic than following i.c.v. treatment with 2DG. These results provide evidence for the transcriptional activation of hypothalamic ORX-A neurons by diminished glucose availability, data that suggest that these cells may function within central pathways that govern adaptive responses to deficits of this substrate fuel. The findings also support the view that a proportion of this phenotypic population is responsive to glucoprivic stimuli of central origin.
有报道称葡萄糖抗代谢物治疗会引发食欲亢进和高血糖，这表明这种能量底物的氧化减少会引发补偿反应，从而提高细胞燃料的可用性。下丘脑外侧区（LHA）的神经元合成食欲肽神经肽，即食欲素-A（ORX-A）。本研究通过调查这些细胞是否会因糖剥夺而表达基因组调节蛋白Fos，来评估食欲素能神经元对低血糖的功能反应性。成年雄性大鼠在腹腔注射（400mg/kg）或脑室内注射（i.c.v.；100μg）抗代谢物2-脱氧-D-葡萄糖（2DG）或生理盐水2小时后处死。从室旁核（PVN）水平到下丘脑后区（PHA）的LHA切片，通过双标免疫细胞化学处理以检测Fos和OXY-A免疫反应性（-ir）。尽管在给予载体后食欲素能神经元表达的Fos-ir可忽略不计，但在两个药物治疗组中，在LHA以及下丘脑背内侧核（DMN）和PHA中均观察到双标的ORX-A神经元。对LHA、DMN和PHA代表性水平的双侧细胞计数显示，在每个结构中，与脑室内注射2DG相比，全身注射2DG后，更大比例的ORX-A神经元被Fos免疫染色。这些结果为葡萄糖可用性降低时下丘脑ORX-A神经元的转录激活提供了证据，这些数据表明这些细胞可能在控制对这种底物燃料缺乏的适应性反应的中枢途径中发挥作用。这些发现还支持这样一种观点，即这一表型群体中的一部分对中枢来源的糖剥夺刺激有反应。
