Developmental changes of leptin receptors in cerebral microvessels: Unexpected relation to leptin transport
Developmental changes of leptin receptors in cerebral microvessels: Unexpected relation to leptin transport
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DOI：
10.1210/en.2007-0893
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发表时间：
2008-03-01
期刊：
影响因子：
4.8
通讯作者：
Kastin, Abba J.
中科院分区：
文献类型：
--
作者：
Pan, Weihong;Hsuchou, Hung;Kastin, Abba J.
脂肪因子瘦素不仅参与成人喂养和肥胖的调节，而且还参与新生儿发育。它通过受体介导的运输穿过血脑屏障（131313）。新生儿和成人血液中的瘦素浓度不同。我们确定了构成血脑屏障的大脑微血管中瘦素受体亚型的发育变化，并检查了它们与血脑屏障中瘦素转运的预期相关性。从1、7、14和60 d龄小鼠富集的大脑微血管中提取总RNA，实时RT-PCR分析瘦素受体亚型。在新生儿脑微血管中，ObRa、ObRb、ObRc和ObRe mRNA均高于成人，但ObRd未检出。下丘脑表现出类似的年龄相关变化，除了成人中更高的ObRb。同源受体gp130在两个区域均未显示出明显的年龄相关变化。尽管瘦素受体增加，但静脉注射后新生儿血脑屏障中瘦素的渗透较少。无血缓冲液原位脑灌注显示，新生儿和成人对瘦素的脑摄取无显著差异，表明瘦素结合蛋白在循环中具有拮抗作用，尤其是可溶性受体ObRe。结果与我们之前的发现一致，即ObRe在培养的内皮细胞中拮抗瘦素的内吞作用和小鼠从血液到脑的运输。总的来说，观察到的瘦素受体的发育变化出乎意料地与瘦素进入大脑无关，这可能表明受体在新生儿和成人中的功能不同。
The adipokine leptin participates not only in the regulation of feeding and obesity in adults but also in neonatal development. It crosses the blood-brain barrier (131313) by receptor-mediated transport. Leptin concentrations in blood differ between neonates and adults. We determined the developmental changes of leptin receptor subtypes in the cerebral microvessels composing the BBB and examined their expected correlation with leptin transport across the BBB. Total RNA was extracted from enriched cerebral microvessels of mice 1, 7,14, and 60 d of age for real-time RT-PCR analysis of leptin receptor subtypes. In cerebral microvessels from neonates, ObRa, ObRb, ObRc, and ObRe mRNA were all higher than in adults, but ObRd was not detectable. Hypothalamus showed similar age-related changes except for ObRb, which was higher in adults. The homologous receptor gp130 did not show significant age-related changes in either region. Despite the increase of leptin receptors, leptin permeation across the BBB after iv injection was less in the neonates. In situ brain perfusion with blood-free buffer showed no significant difference in the brain uptake of leptin between neonates and adults, indicating an antagonistic role of leptin-binding proteins in the circulation, especially the soluble receptor ObRe. The results are consistent with our previous finding that ObRe antagonizes leptin endocytosis in cultured endothelia and transport from blood to brain in mice. Overall, the developmental changes observed for leptin receptors unexpectedly failed to correlate with the entry of leptin into brain, and this may indicate different functions of the receptors in neonates and adults.