Synaptic plasticity in energy balance regulation.
Synaptic plasticity in energy balance regulation.
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DOI：
10.1038/oby.2006.314
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发表时间：
2006-08-01
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影响因子：
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通讯作者：
Horvath, Tamas L
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作者：
Horvath, Tamas L
瘦素通过调节下丘脑弓状核中神经肽Y（NPY）和阿黑皮素原（POMC）神经元的活性来调节能量平衡。瘦素缺陷型（ob/ob）小鼠与野生型小鼠的不同之处在于兴奋性和抑制性突触后密度的数量以及NPY和POMC神经元上的电流。当瘦素被传递到ob/ob小鼠时，突触密度迅速正常化，在6小时内可检测到这种效果，比瘦素对食物摄入的影响早几个小时。在瘦素替代的ob/ob小鼠中，突触电流也向野生型值移动。这些数据表明，瘦素介导的可塑性在ob/ob下丘脑可能是一些激素的行为效应的基础。为了确定所观察到的突触可塑性是否是瘦素特异性的，我们分析了促食欲激素ghrelin和促食欲激素雌二醇的作用。Ghrelin重排野生型动物的突触，以支持抑制POMC的紧张，而雌二醇引发了大量的兴奋性，谷氨酸输入的POMC神经元的数量增加。雌二醇引起的突触重排不依赖于瘦素，因为它在瘦素-（ob/ob）和瘦素受体缺陷（db/db）小鼠中也很明显，并且在这些突变肥胖动物中随着食物摄入量减少和能量消耗增加而增加。这种可塑性也观察到在其他下丘脑区域和下丘脑外的网站。这些观察结果提出了这样一个概念，即突触可塑性是外周代谢激素影响大脑功能的主要途径。
Leptin regulates energy balance, in part, by modulating the activity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus. Leptin-deficient (ob/ob) mice differ from wild-type mice in the number of excitatory and inhibitory post-synaptic densities and currents onto NPY and POMC neurons. When leptin was delivered to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake. Synaptic currents were also shifted toward wild-type values in leptin-replaced ob/ob mice. These data suggest that leptin-mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's behavioral effects. In an effort to determine whether the observed synaptic plasticity is leptin specific, we analyzed the effects of an orexigenic hormone, ghrelin, and anorexigenic hormone, estradiol. Ghrelin rearranged synapses in wild type animals to support suppressed POMC tone, whereas the estradiol triggered a robust increase in the number of excitatory, glutamate inputs of POMC neurons. The rearrangement of synapses by estradiol was leptin independent, because it was also evident in leptin- (ob/ob) and leptin receptor-deficient (db/db) mice and was paralleled with decreased food intake and increased energy expenditure in these mutant, obese animals. Such plasticity was also observed in other hypothalamic regions and extrahypothalamic sites. These observations raise the notion that synaptic plasticity is a major way through which peripheral metabolic hormones influence brain functions.