Dunn-Meynell A A, Govek E, Levin B E
Neurology Service, DVA Medical Center, E. Orange, NJ 07018, USA.
Brain Res. 1997 Feb 14;748(1-2):100-6. doi: 10.1016/s0006-8993(96)01280-2.
Perfusion of the forebrain with glucose at concentrations which alter neither plasma insulin nor glucose levels leads to sympathetic activation in some rats. We used the expression of Fos-like immunoreactivity (FLI) as an index of neuronal activation to examine the anatomic substrate underlying this phenomenon. Male Sprague-Dawley rats were infused via the right internal carotid artery with glucose (4 mg/kg/min) or equiosmolar mannitol for 60 min. They were killed 3 h after infusion onset and their brains reacted for FLI. As compared to mannitol-infused controls, 105% and 117% more neurons in hypothalamic ventromedial nucleus (VMN) and parvocellular portion of the paraventricular nuclei (PVN) of glucose-infused rats showed FLI, respectively. Importantly, only about half the glucose-infused rats showed increased FLI cells in these areas when compared to controls. In these same animals, glucose also significantly activated cells in the dorsomedial n. There was little FLI expressed in the magnocellular neurons of the PVN. This selective glucose response was bilateral in keeping with the bilateral distribution of India ink to midline hypothalamic structures following unilateral carotid infusions. Retrograde transport of cholera toxin B from medullary and thoracic spinal cord sympathetic outflow areas showed labeling of about 10% of PVN neurons with FLI activated by intracarotid glucose. There was no double labeling of VMN neurons. This supports the presence of anatomic pathways by which a subpopulation of glucose responsive PVN neurons might activate the sympathetic outflow areas in the medulla and spinal cord. The apparent bimodal distribution of glucose-induced activation of VMN and PVN neurons is in keeping with a similar bimodal pattern of sympathetic activation which obesity-prone but not obesity-resistant rats show following glucose infusions. Taken together, these data support a role for glucose-sensitive VMN and parvocellular PVN neurons in the weight gain phenotype specific sympathetic activation to glucose.
用既不改变血浆胰岛素水平也不改变血糖水平的浓度的葡萄糖灌注前脑，会导致一些大鼠出现交感神经激活。我们使用Fos样免疫反应性（FLI）的表达作为神经元激活的指标，来研究这一现象背后的解剖学基础。雄性Sprague-Dawley大鼠通过右颈内动脉输注葡萄糖（4mg/kg/分钟）或等渗甘露醇60分钟。输注开始3小时后将它们处死，其大脑进行FLI反应。与输注甘露醇的对照组相比，输注葡萄糖的大鼠下丘脑腹内侧核（VMN）和室旁核小细胞部（PVN）中显示FLI的神经元分别多105%和117%。重要的是，与对照组相比，只有约一半输注葡萄糖的大鼠在这些区域显示FLI细胞增加。在这些相同的动物中，葡萄糖还显著激活了背内侧核中的细胞。PVN的大细胞神经元中几乎没有FLI表达。这种选择性葡萄糖反应是双侧的，这与单侧颈动脉输注后印度墨汁向中线下丘脑结构的双侧分布一致。霍乱毒素B从延髓和胸段脊髓交感神经传出区域的逆行运输显示，约10%的PVN神经元被颈内动脉注射葡萄糖激活并带有FLI标记。VMN神经元没有双重标记。这支持了存在解剖学通路，通过该通路，一部分对葡萄糖有反应的PVN神经元可能激活延髓和脊髓中的交感神经传出区域。VMN和PVN神经元的葡萄糖诱导激活的明显双峰分布与肥胖倾向但非肥胖抵抗大鼠在输注葡萄糖后显示的类似双峰交感神经激活模式一致。综上所述，这些数据支持葡萄糖敏感的VMN和PVN小细胞神经元在体重增加表型中对葡萄糖的特异性交感神经激活中起作用。
