Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice
Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice
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DOI：
10.1210/en.2010-0681
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发表时间：
2010-11-01
期刊：
影响因子：
4.8
通讯作者：
Diano, Sabrina
中科院分区：
文献类型：
--
作者：
Gyengesi, Erika;Liu, Zhong-Wu;Diano, Sabrina
循环激素（例如瘦素和生长素释放肽）的变化会引起突触输入组织和下丘脑弓状核神经元电生理特性的改变。为了评估循环糖皮质激素的变化是否也会改变突触排列和膜电位特性，我们研究了小鼠肾上腺切除术（ADX）和皮质酮替代疗法对下丘脑弓状核的阿黑皮质素原（POMC）和神经肽Y（NPY）/刺鼠相关蛋白（AgRP）神经元的影响。 ADX 减少了 POMC 神经元上对称的、假定的抑制性突触的数量，以及 NPY/AgRP 神经元上的不对称的、假定的兴奋性突触的数量。将 ADX 小鼠体内的皮质酮替换至与假手术动物相似的水平后，POMC 和 NPY/AgRP 神经元上的突触数量恢复到假手术对照中的水平。 ADX 小鼠突触排列的改变并不是由于食物摄入量的减少所致，这一点通过对配对喂养的对照动物的突触分析得到证明。与突触输入组织的改变一致，与假手术对照组相比，ADX 小鼠中观察到 POMC 膜电位去极化和 NPY/AgRP 膜电位超极化。所有这些变化在皮质酮替代后都会恢复。这些结果表明，皮质类固醇已知的促食欲作用至少部分是由突触变化和黑皮质素系统兴奋性改变介导的。 （内分泌学151：5395-5402，2010）
Changes in circulating hormones, such as leptin and ghrelin, induce alterations in synaptic input organization and electrophysiological properties of neurons of the arcuate nucleus of the hypothalamus. To assess whether changes in circulating glucocorticoids also alter synaptic arrangement and membrane potential properties, we studied the effect of adrenalectomy (ADX) and corticosterone replacement in mice on the proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus. ADX reduced the number of symmetric, putative inhibitory synapses onto POMC neurons and the number of asymmetric, putative excitatory synapses onto NPY/AgRP neurons. Corticosterone replacement in ADX mice to levels similar to sham-operated animals restored the number of synapses onto POMC and NPY/AgRP neurons to that seen in sham-operated controls. The alterations in the synaptic arrangement in ADX mice were not due to their decrease in food intake as evidenced by the synaptic analysis of the pair-fed control animals. In line with the altered synaptic input organization, a depolarization of POMC membrane potential and a hyperpolarization of NPY/AgRP membrane potential were observed in ADX mice compared with their sham-operated controls. All of these changes reverted upon corticosterone replacement. These results reveal that the known orexigenic action of corticosteroids is mediated, at least in part, by synaptic changes and altered excitability of the melanocortin system. (Endocrinology 151: 5395-5402, 2010)