Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat
Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat
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DOI：
10.1152/ajpregu.90690.2008
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发表时间：
2009-03-01
影响因子：
2.8
通讯作者：
Ozanne, S. E.
中科院分区：
文献类型：
--
作者：
Cottrell, E. C.;Cripps, R. L.;Ozanne, S. E.
科特雷尔EC，Cripps RL，Duncan JS，Barrett P，Mercer JG，Herwig A，Ozanne SE。下丘脑瘦素受体的发育变化：与出生后大鼠瘦素激增和能量平衡神经肽的关系。Am J Physiol Regul Integr Comp Physiol 296：R631-R639,2009。2009年1月14日首次出版；DOI：10.1152/ajpregu.90690.2008-在成人大脑中，瘦素主要通过影响食物摄取和能量消耗的下丘脑回路来调节能量稳态。来自啮齿动物模型的证据表明，在出生后的早期生命中，瘦素在调节这些途径方面相对无效，尽管循环中的瘦素水平很高，而且中枢神经系统中存在瘦素受体。此外，近年来，瘦素在建立能量平衡回路中的神经营养作用已经出现。瘦素发挥这些作用的确切方式，以及瘦素的作用部位，目前尚不清楚。为了详细描述出生后大鼠能量平衡系统的发育与瘦素浓度的关系，采用原位杂交的方法，测定了内源性瘦素水平，以及下丘脑内侧基底核瘦素受体和能量平衡神经肽的基因表达。出生后早期，弓状核中瘦素受体、食欲神经肽和厌食神经肽的表达均增加。在出生后第4天(P4)，我们在第三脑室室管膜细胞(3V)检测到密集的瘦素受体表达，在出生后第一周表现出显著的减少，与该区域明显的形态变化相一致。急性瘦素攻击强烈地诱导了P4动物3V中细胞因子信号转导-3的表达抑制，但不是P14动物，这表明在这一时期瘦素作用的位置发生了明显的变化。这些发现表明，瘦素的神经营养作用可能涉及出生后发育受限时期的3V信号。
Cottrell EC, Cripps RL, Duncan JS, Barrett P, Mercer JG, Herwig A, Ozanne SE. Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat. Am J Physiol Regul Integr Comp Physiol 296: R631-R639, 2009. First published January 14, 2009; doi: 10.1152/ajpregu.90690.2008.- In the adult brain, leptin regulates energy homeostasisprimarily via hypothalamic circuitry that affects food intake and energy expenditure. Evidence from rodent models has demonstrated that during early postnatal life, leptin is relatively ineffective in modulating these pathways, despite the high circulating levels and the presence of leptin receptors within the central nervous system. Furthermore, in recent years, a neurotrophic role for leptin in the establishment of energy balance circuits has emerged. The precise way in which leptin exerts these effects, and the site of leptin action, is unclear. To provide a detailed description of the development of energy balance systems in the postnatal rat in relation to leptin concentrations during this time, endogenous leptin levels were measured, along with gene expression of leptin receptors and energy balance neuropeptides in the medial basal hypothalamus, using in situ hybridization. Expression of leptin receptors and both orexigenic and anorexigenic neuropeptides increased in the arcuate nucleus during the early postnatal period. At postnatal day 4 (P4), we detected dense leptin receptor expression in ependymal cells of the third ventricle (3V), which showed a dramatic reduction over the first postnatal weeks, coinciding with marked morphological changes in this region. An acute leptin challenge robustly induced suppressor of cytokine signaling-3 expression in the 3V of P4 but not P14 animals, revealing a clear change in the location of leptin action over this period. These findings suggest that the neurotrophic actions of leptin may involve signaling at the 3V during a restricted period of postnatal development.