Permeability of the blood-brain barrier to albumin and insulin in the young and aged SAMP8 mouse
Permeability of the blood-brain barrier to albumin and insulin in the young and aged SAMP8 mouse
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DOI：
10.1093/gerona/55.12.b601
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发表时间：
2000-12-01
影响因子：
5.1
通讯作者：
Morley, JE
中科院分区：
文献类型：
--
作者：
Banks, WA;Farr, SA;Morley, JE
阿尔茨海默病中出现的胰岛素脑脊液/血清比率下降被认为是脑葡萄糖利用受到干扰的一种机制。胰岛素通过一个系统转运穿过血脑屏障（BBB），该系统会因病理生理事件而改变。我们使用SAMP 8小鼠，一种在8-12个月大时出现严重学习和记忆缺陷的品系，以确定胰岛素转运蛋白或BBB完整性是否随着年龄的增长而改变。通过静脉注射放射性白蛋白，在17小时后冲洗血管间隙，并测量脑/血清比率来测量BBB完整性。这种非常灵敏的方法发现，在年轻和老年SAMP 8小鼠中，血脑屏障对白蛋白的渗透性没有增加。这与先前在阿尔茨海默病患者和其他SAMP 8小鼠群体中的研究进行了比较，这些研究发现了BBB破坏的证据。对于放射性标记的胰岛素，我们使用多时间回归分析来测量单向流入率（Ki）和与脑内皮的可逆结合（Vi）。老年SAMP 8小鼠的全脑转运率无显著下降。Ki和Vi值显着不同的大脑区域和Ki的丘脑和Vi的小脑和丘脑在老年小鼠较高。我们的结论是，BBB的完整性或BBB胰岛素转运蛋白的活性的改变并不构成老年SAMP 8小鼠学习和记忆缺陷的基础。
The decrease in the insulin cerebrospinal fluid/serum ratio seen in Alzheimer's disease has been suggested as a mechanism by which brain glucose utilization could be perturbed. Insulin is transported across the blood-brain barrier (BBB) by a system that is altered by pathophysiological events. We used SAMP8 mice, a strain that by 8-12 months of age develops severe deficits in learning and memory, to determine whether the insulin transporter or BBB integrity was altered with aging. BBB integrity was measured by injecting radioactive albumin intravenously, washing out the vascular space up to 17 hours later, and measuring brain/serum ratios. This very sensitive method found no increase in the permeability of the BBB to albumin in young and aged SAMP8 mice. This compares with previous studies in humans with Alzheimer's disease and in other colonies of SAMP8 mice that have found evidence for BBB disruption. For radioactively labeled insulin, we used multiple-time regression analysis to measure both the unidirectional influx rate (Ki) and the reversible binding to brain endothelium (Vi). A nonsignificant decrease in the transport rate for whole brain occurred in aged SAMP8 mice. Ki and Vi values significantly varied among brain regions and the Ki for the thalamus and the Vi for the cerebellum and thalamus were higher in aged mice. We conclude that alterations in BBB integrity or the activity of the BBB insulin transporter do not underlie the deficits in learning and memory seen in the aged SAMP8 mouse.