Hoyda Ted D, Smith Pauline M, Ferguson Alastair V
Department of Physiology, Faculty of Arts and Science, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Brain Res. 2009 Feb 23;1256:76-84. doi: 10.1016/j.brainres.2008.12.012. Epub 2008 Dec 11.
Adiponectin is an adipocyte derived hormone which acts in the CNS to control autonomic function, energy and cardiovascular homeostasis. Two 7-transmembrane domain receptors, AdipoR1 and AdipoR2, expressed in the hypothalamus and brainstem mediate the actions of adiponectin. The medulla's nucleus of the solitary tract (NTS) is the primary viscerosensory integration site and an important nucleus in the regulation of cardiovascular function. Here we show the localization of both AdipoR1 and AdipoR2 mRNA in the NTS. We have investigated the consequences of receptor activation in response to exogenous application of adiponectin on cardiovascular (blood pressure and heart rate monitoring in vivo), and single neuron (whole cell current-clamp recordings in vitro) function. Microinjection of adiponectin in the medial NTS (mNTS) at the level of the area postrema resulted in a decrease in BP (mean AUC= -2055+/-648.1, n=5, mean maximum effect: -11.7+/-3.6 mm Hg) while similar commissural NTS (cNTS) microinjections were without effect. Patch clamp recordings from NTS neurons in a medullary slice preparation showed rapid (within 200 s of application) reversible (usually within 1000 s following washout) effects of adiponectin on the membrane potential of 62% of mNTS neurons tested (38/61). In 34% (n=21) of mNTS neurons adiponectin induced a depolarization of membrane potential (6.8+/-0.9 mV), while the remainder of mNTS cells influenced by adiponectin (n=17) hyperpolarized in response to this adipokine (-5.4+/-0.7 mV). Post-hoc single cell RT-PCR (ssRT-PCR) analysis of neurons showed that the majority of NPY mRNA positive mNTS neurons were depolarized by adiponectin (7/11), while 4 of these depolarized cells were also GAD67 positive. The results presented in this study suggest adiponectin acts in the NTS to control BP and suggest that such effects may occur as a direct result of the ability of this adipokine to modulate the excitability of discrete groups of neurons in the NTS. These studies identify the mNTS as a new CNS site which adiponectin may act to influence central autonomic processing.
脂联素是一种由脂肪细胞分泌的激素，它在中枢神经系统中发挥作用，以控制自主功能、能量和心血管稳态。两种7跨膜结构域受体，脂联素受体1（AdipoR1）和脂联素受体2（AdipoR2），在下丘脑和脑干中表达，介导脂联素的作用。延髓孤束核（NTS）是主要的内脏感觉整合位点，也是调节心血管功能的重要核团。在这里，我们展示了AdipoR1和AdipoR2 mRNA在NTS中的定位。我们研究了对外源性脂联素的反应中受体激活对心血管（体内血压和心率监测）和单个神经元（体外全细胞电流钳记录）功能的影响。在最后区水平的内侧NTS（mNTS）中微量注射脂联素导致血压下降（平均AUC = -2055±648.1，n = 5，平均最大效应：-11.7±3.6 mmHg），而类似的联合NTS（cNTS）微量注射则没有效果。在延髓切片制备中对NTS神经元进行膜片钳记录显示，脂联素对62%（38/61）测试的mNTS神经元的膜电位有快速（给药后200秒内）可逆（通常在洗脱后1000秒内）的影响。在34%（n = 21）的mNTS神经元中，脂联素诱导膜电位去极化（6.8±0.9 mV），而其余受脂联素影响的mNTS细胞（n = 17）对这种脂肪因子产生超极化反应（-5.4±0.7 mV）。对神经元进行事后单细胞逆转录聚合酶链反应（ssRT-PCR）分析表明，大多数NPY mRNA阳性的mNTS神经元被脂联素去极化（7/11），而这些去极化细胞中有4个也是GAD67阳性。本研究结果表明脂联素在NTS中发挥作用以控制血压，并表明这种作用可能是由于这种脂肪因子调节NTS中离散神经元群兴奋性的能力直接导致的。这些研究确定mNTS是脂联素可能作用以影响中枢自主神经处理的一个新的中枢神经系统位点。
