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葡萄糖缺乏诱导下丘脑多巴胺能神经元中Fos免疫反应性

Glucoprivic induction of Fos immunoreactivity in hypothalamic dopaminergic neurons.

作者信息

Briski K P

机构信息

Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164, USA.

出版信息

Neuroreport. 1998 Jan 26;9(2):289-95. doi: 10.1097/00001756-199801260-00021.

DOI:10.1097/00001756-199801260-00021
PMID:9507971
Abstract

The hypothalamic neurotransmitter dopamine (DA) regulates pituitary secretion of the glucoregulatory hormones, growth hormone (GH) and adrenocorticotropin (ACTH). The glucose antimetabolite, 2-deoxy-D-glucose (2DG), elicits expression of the proto-oncogene product Fos, which is expressed in hypothalamic structures where DA is synthesized. These studies utilized dual-label immunocytochemistry to determine whether discrete DA neuron populations in this region of the brain exhibit Fos immunoreactivity (-ir) in response to glucopenia. Ovariectomized female rats implanted s.c. with exogenous estradiol or vehicle were injected with 2DG (400 mg/kg, i.p.) or saline, and sacrificed 2 h later. Whereas Fos-ir was negligible after saline administration, 2DG induced expression of Fos-ir by TH-ir neurons in the paraventricular (PVN), periventricular (Pe) and arcuate nuclei (ARC), and in the anterior hypothalamic area (AHA). TH-ir neurons in the zona incerta did not express Fos-ir following 2DG. Although mean numbers of co-labeled neurons in the Pe, PVN and AHA did not differ between estradiol- and non-steroid-treated rats, the former group exhibited significantly higher numbers of TH-positive plus Fos-positive neurons in the ARC in response to 2DG. These results reveal the functional responsiveness of discrete DA neuron populations to glucoprivation, and indicate that estradiol enhances cellular accumulation of Fos-ir by ARC DA neurons during this metabolic challenge.

摘要

下丘脑神经递质多巴胺(DA)调节垂体分泌葡萄糖调节激素、生长激素(GH)和促肾上腺皮质激素(ACTH)。葡萄糖抗代谢物2-脱氧-D-葡萄糖(2DG)可引发原癌基因产物Fos的表达,Fos在合成DA的下丘脑结构中表达。这些研究利用双标记免疫细胞化学来确定大脑该区域中离散的DA神经元群体是否会因低血糖而表现出Fos免疫反应性(-ir)。给皮下植入外源性雌二醇或赋形剂的去卵巢雌性大鼠腹腔注射2DG(400mg/kg)或生理盐水,2小时后处死。生理盐水给药后Fos-ir可忽略不计,而2DG可诱导室旁核(PVN)、室周核(Pe)、弓状核(ARC)以及下丘脑前区(AHA)中TH-ir神经元表达Fos-ir。未定带中的TH-ir神经元在注射2DG后不表达Fos-ir。虽然雌二醇处理组和非类固醇处理组大鼠的Pe、PVN和AHA中共同标记神经元的平均数量没有差异,但前一组在注射2DG后ARC中TH阳性加Fos阳性神经元的数量显著更高。这些结果揭示了离散的DA神经元群体对糖剥夺的功能反应性,并表明在这种代谢挑战期间,雌二醇可增强ARC中DA神经元Fos-ir的细胞积累。

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