Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event
Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event
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DOI：
10.1677/jme.1.01819
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发表时间：
2005-08-01
影响因子：
3.5
通讯作者：
Adan, RAH
中科院分区：
文献类型：
--
作者：
Kas, MJH;Bruijnzeel, AW;Adan, RAH
应激影响啮齿动物和人类的进食行为，这表明能量平衡的调节和应激反应是耦合的生理过程。神经肽Y（NPY）和刺鼠相关蛋白（AgRP）是两种强食物刺激性神经肽，在下丘脑弓状核神经元中高度共定位。最近的研究表明，这些神经元中的NPY和AgRP mRNA水平对禁食和瘦素的反应类似，表明这些食欲神经元中神经肽系统的功能冗余。然而，我们已经发现，在弓状核神经元的NPY和AgRP mRNA的表达分离后立即应激事件。在短暂的不可避免的足部电击后2小时，AgRP mRNA水平下调（P < 0（.）0001）。与此相反，NPY mRNA表达上调（P < 0（.）0001）。为了提供AgRP（黑皮质素受体的反向激动剂）的这种急性下调的生理相关性，我们已经表明，急性脑室内注射黑皮质素受体激动剂，α-黑素细胞刺激激素（α-MSH），引起下丘脑-垂体-肾上腺-皮质（HPA）轴在应激事件后比对照组明显更强的激活。因此，在类似的弓状核神经元中，AgRP和NPY mRNA水平在应激事件后受到不同的调节。这可能有助于在反复的应激经历后增加a-MSH激活HPA轴的敏感性。
Stress affects eating behaviour in rodents and humans, suggesting that the regulation of energy balance and the stress response are coupled physiological processes. Neuropeptide Y (NPY) and agouti-related protein (AgRP) are potent food-stimulating neuropeptides that are highly co-localised in arcuate nucleus neurons of the hypothalamus. Recent studies have shown that NPY and AgRP mRNA levels in these neurons respond similarly to fasting and leptin, indicating functional redundancy of the neuropeptide systems in these orexigenic neurons. However, we have found that NPY and AgRP mRNA expression in arcuate nucleus neurons are dissociated immediately following a stressful event. Two hours following a brief session of inescapable foot shocks, AgRP mRNA levels are down-regulated (P < 0(.)0001). In contrast, NPY mRNA levels are up-regulated (P < 0(.)0001). To provide physiological relevance for this acute down-regulation of AgRP, an inverse agonist of melanocortin receptors, we have shown that acute intracerebroventricular injection of a melanocortin receptor agonist, a-melanocyte-stimulating hormone (alpha-MSH), caused a significantly stronger activation of the hypothalamus-pituitary-adrenal-cortical (HPA) axis following a stressful event than in controls. Thus, AgRP and NPY mRNA levels in similar arcuate nucleus neurons are differentialiy regulated following a stressful event. This may contribute to increased sensitivity for a-MSH to activate the HPA axis following a repeated stressful experience.