Briski K P, Marshall E S
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, 71209-0470, USA.
Neurochem Res. 2001 Jul;26(7):783-92. doi: 10.1023/a:1011655901032.
Reports that food intake is stimulated by intracerebroventricular (i.c.v.) administration of the SGLT1 Na+-D-glucose cotransport inhibitor, phlorizin, suggest that decreased central glucose uptake is a stimulus for compensatory motor activity underlying restoration of energy imbalance. In order to identify central cell populations that are functionally responsive to decreased SGLT1 function in the brain, the present study utilized immunocytochemical techniques to demonstrate cellular expression of the inducible activator protein-1 transcription factor, Fos, following i.c.v. delivery of phlorizin. Groups of adult male rats were treated with phlorizin at a dose of 10, 50, or 250 microg/animal, then sacrificed 2 hr later by transcardial perfusion. Ependymal expression of Fos-immunoreactivity (-ir) was observed throughout most of the cerebroventricular system, except the medullary fourth ventricle, at each dose examined. Higher doses of the transport inhibitor elicited immunostaining of periventricular glia, characterized by cytoplasmic glial fibrillary acidic protein-ir, underlying the lateral, third, and rostral fourth ventricles and cerebral aqueduct. These doses also resulted in the transcriptional activation of neurons in discrete brain sites, including the rostral medial preoptic area, median preoptic n., preoptic and hypothalamic periventricular n., subfornical organ, thalamic medial habenular and paraventricular n., hypothalamic paraventricular, ventromedial, and arcuate n., and n. of the solitary tract. These results show that nonexcitable cells located throughout much of the central neuroaxis and discrete populations of neurons in the brain are genomically responsive to pharmacological inhibition of central SGLT1 function. Evidence for the functional responsiveness of these cell types to manipulation of energy-dependent glucose transport suggests that cellular uptake of this metabolic fuel may serve as an indicator of central energy substrate availability, and that alterations in glucose uptake via this specific mechanism may be the source of regulatory signals involved in the maintenance of energy homeostasis.
有报道称，脑室内（i.c.v.）注射钠葡萄糖协同转运蛋白1（SGLT1）抑制剂根皮苷可刺激食物摄入，这表明中枢葡萄糖摄取减少是能量失衡恢复过程中代偿性运动活动的刺激因素。为了确定大脑中对SGLT1功能降低有功能反应的中枢细胞群，本研究利用免疫细胞化学技术，在脑室内注射根皮苷后，证明诱导型激活蛋白-1转录因子Fos的细胞表达。成年雄性大鼠分组接受10、50或250微克/只剂量的根皮苷治疗，2小时后通过心脏灌注处死。在所检测的每个剂量下，除了延髓第四脑室，在大部分脑室系统中均观察到Fos免疫反应性（-ir）的室管膜表达。较高剂量的转运抑制剂引起室周神经胶质细胞免疫染色，其特征为细胞质胶质纤维酸性蛋白-ir，位于侧脑室、第三脑室、第四脑室前部和中脑导水管下方。这些剂量还导致离散脑区的神经元转录激活，包括视前内侧区前部、视前正中核、视前和下丘脑室周核、穹窿下器官、丘脑内侧缰核和室旁核、下丘脑室旁核、腹内侧核和弓状核以及孤束核。这些结果表明，位于中枢神经轴大部分区域的非兴奋性细胞以及大脑中离散的神经元群体对中枢SGLT1功能的药理学抑制具有基因组反应。这些细胞类型对能量依赖性葡萄糖转运操纵的功能反应证据表明，这种代谢燃料的细胞摄取可能作为中枢能量底物可用性的指标，并且通过这种特定机制的葡萄糖摄取改变可能是参与维持能量稳态的调节信号的来源。
