Actions of adiponectin on the excitability of subfornical organ neurons are altered by food deprivation
Actions of adiponectin on the excitability of subfornical organ neurons are altered by food deprivation
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DOI：
10.1016/j.brainres.2010.02.076
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发表时间：
2010-05-12
期刊：
影响因子：
2.9
通讯作者：
Ferguson, Alastair V.
中科院分区：
文献类型：
--
作者：
Alim, Ishraq;Fry, W. Mark;Ferguson, Alastair V.
脂联素(ADP)是一种由脂肪组织产生的多肽，是一种胰岛素增敏激素。最近的研究表明，脂联素受体(AdipoR1和AdipoR2)存在于中枢神经系统，尽管脂联素确实存在于循环和脑脊液中，但对于ADP是否能通过血脑屏障(BBB)仍存在一些争论。室周器官(CVO)是缺乏正常血脑屏障的中枢神经系统部位，是循环脂联素直接影响中枢神经系统的部位。穹隆下器(SFO)是一种参与能量平衡调节的CVO，其机制是SFO神经元对包括胰淀素、CCK、PYY和Ghrelin在内的多种循环饱足信号作出反应。我们最近的微阵列分析表明，在SFO中存在脂联素受体。我们在这里报道，SFO显示出高密度的脂联素受体(AdipoR1和AdipoR2)的mRNA，并且ADP影响分离的SFO神经元的兴奋性。单独亚群的SFO神经元在10 nM ADP作用下，要么去极化(8.9+/-0.9 mV，97个细胞)，要么超极化(-8.0+/-0.5 mV，34/97个细胞)，这种效应是浓度依赖且可逆的。我们的微阵列分析还表明，48h的食物剥夺导致了AdipoR2基因表达的特异性增加(对AdipoR1mRNA没有影响)，我们在这里用实时荧光定量PCR技术证实了这一点。食物剥夺也改变了SFO神经元对脂联素的反应性，77%(8/11)的细胞对脂联素有去极化反应，但没有观察到超极化。这些观察结果支持这样一个概念，即SFO可能是感知循环ADP并将这些信息传输到参与调节能量平衡的关键中枢神经系统部位的关键参与者。皇冠版权所有(C)2010由爱思唯尔出版。保留所有权利。
Adiponectin (ADP) is a peptide produced by adipose tissue, which acts as an insulin sensitizing hormone. Recent studies have shown that adiponectin receptors (AdipoR1 and AdipoR2) are present in the CNS, and although adiponectin does appear in both circulation and the cerebrospinal fluid there is still some debate as to whether or not ADP crosses the blood brain barrier (BBB). Circumventricular organs (CVO) are CNS sites which lack normal BBB, and thus represent sites at which circulating adiponectin may act to directly influence the CNS. The subfornical organ (SFO) is a CVO that has been implicated in the regulation of energy balance as a consequence of the ability of SFO neurons to respond to a number of different circulating satiety signals including amylin, CCK, PYY and ghrelin. Our recent microarray analysis suggested the presence of adiponectin receptors in the SFO. We report here that the SFO shows a high density of mRNA for both adiponectin receptors (AdipoR1 and AdipoR2), and that ADP influences the excitability of dissociated SFO neurons. Separate subpopulations of SFO neurons were either depolarized (8.9 +/- 0.9 mV, 21 of 97 cells), or hyperpolarized (-8.0 +/- 0.5 mV, 34 of 97 cells), by bath application of 10 nM ADP, effects which were concentration dependent and reversible. Our microarray analysis also suggested that 48 h of food deprivation resulted in specific increases in AdipoR2 mRNA expression (no effect on AdipoR1 mRNA), observations which we confirm here using real-time PCR techniques. The effects of food deprivation also resulted in a change in the responsiveness of SFO neurons to adiponectin with 77% (8/11) of cells tested responding to adiponectin with depolarization, while no hyperpolarizations were observed. These observations support the concept that the SFO may be a key player in sensing circulating ADP and transmitting such information to critical CNS sites involved in the regulation of energy balance. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.