Pan Weihong, Barron Misty, Hsuchou Hung, Tu Hong, Kastin Abba J
Blood-Brain Barrier Lab, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Neuropsychopharmacology. 2008 Mar;33(4):859-66. doi: 10.1038/sj.npp.1301452. Epub 2007 May 9.
Leptin, a polypeptide mainly produced in the periphery, crosses the blood-brain barrier (BBB) by receptor-mediated transport to exert multiple central nervous system actions including decreased food intake. The reciprocal interactions between leptin transport and alcohol drinking are not clear. In this study, we tested whether alcohol increases leptin entry into brain and, if this occurs, whether it is a consequence of a generalized increase in the permeability of the BBB. BBB permeability to albumin, the increased permeation of which indicates BBB disruption, as well as to leptin was measured after alcohol ingestion. CD1 and B6 mice ingested a 5% liquid alcohol diet or its isocaloric control for 2 weeks. Alcohol ingestion resulted in increased blood-alcohol levels, decreased blood-leptin concentrations, and increased permeation of radioactively labeled leptin across the BBB as shown by in situ perfusion. Although the increased influx of the vascular marker albumin into brain showed partial disruption of the BBB, the influx of (125)I-leptin still could be suppressed by excess unlabeled leptin, indicating persistence of its saturable transport system. When given a choice of either alcohol or control diet, even the alcohol-preferring B6 mice showed a significantly greater preference for the control liquid diet, and there was no evidence of BBB disruption or alterated leptin transport. Furthermore, acute alcohol intoxication induced by intraperitoneal injection of 20% alcohol did not result in BBB disruption or increased leptin permeation 4 h later. Thus, partial disruption of the BBB and increased permeation of leptin in both CD1 and B6 mice were only induced by chronic alcohol ingestion. The results showing increased leptin permeation across the BBB lead to the speculation that leptin may serve as a homeostatic feeding signal in these mice.
瘦素是一种主要在外周产生的多肽，它通过受体介导的转运穿过血脑屏障（BBB），以发挥多种中枢神经系统作用，包括减少食物摄入。瘦素转运与饮酒之间的相互作用尚不清楚。在本研究中，我们测试了酒精是否会增加瘦素进入大脑的量，如果是这样，这是否是血脑屏障通透性普遍增加的结果。在摄入酒精后，测量了血脑屏障对白蛋白（其通透性增加表明血脑屏障破坏）以及对瘦素的通透性。CD1和B6小鼠摄入5%的液体酒精饮食或其等热量对照饮食2周。如原位灌注所示，摄入酒精导致血酒精水平升高、血瘦素浓度降低以及放射性标记的瘦素穿过血脑屏障的通透性增加。尽管血管标记物白蛋白进入大脑的增加表明血脑屏障有部分破坏，但过量未标记的瘦素仍可抑制（125）I-瘦素的流入，表明其可饱和转运系统仍然存在。当在酒精或对照饮食之间进行选择时，即使是偏好酒精的B6小鼠也对对照液体饮食表现出明显更高的偏好，并且没有血脑屏障破坏或瘦素转运改变的证据。此外，腹腔注射20%酒精诱导的急性酒精中毒在4小时后并未导致血脑屏障破坏或瘦素通透性增加。因此，只有慢性摄入酒精才会诱导CD1和B6小鼠血脑屏障的部分破坏和瘦素通透性增加。瘦素穿过血脑屏障的通透性增加的结果导致推测瘦素可能在这些小鼠中作为一种稳态进食信号。
