Age-related changes in choroid plexus and blood-cerebrospinal fluid barrier function in the sheep
Age-related changes in choroid plexus and blood-cerebrospinal fluid barrier function in the sheep
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DOI：
10.1016/j.exger.2008.12.004
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发表时间：
2009-04-01
影响因子：
3.9
通讯作者：
Preston, J. E.
中科院分区：
文献类型：
--
作者：
Chen, R. L.;Kassem, N. A.;Preston, J. E.
脉络膜丛（CPs）和血脑脊液屏障（BCSFB）功能障碍可能导致与年龄相关的认知能力下降和神经退行性疾病。我们使用幼年（1-2岁）、中年（3-6岁）和老年（7-10岁）羊的CP，探讨衰老对CP和BCSFB各方面功能的影响。老年羊的脑脊液（CSF）总蛋白明显高于年轻羊，而原位灌注的CP在老年羊和中年羊的脑脊液分泌量明显低于年轻羊，这与CP对Na-22（+）的摄取和排出减少有关。与幼龄动物相比，老年动物的CPs明显更高；然而，高分子量标记物（125）l-牛血清白蛋白的稳态提取没有显著差异。这表明老羊对中小分子BCSFB的被动通透性增加。根据MTT测定，老龄动物的CP氧化还原活性显著降低，然而，随着年龄的增长，CP的ATP含量和能量电荷没有显著差异，这表明有足够的基线能量储备能力。这些数据表明，正常的衰老过程会改变脑脊液中的蛋白质含量、脑脊液分泌、BCSFB的完整性和上皮层的Na+通量，从而影响脑脊液的稳态和周转。(C) 2008爱思唯尔公司版权所有。
Dysfunction of the choroid plexuses (CPs) and the blood-cerebrospinal fluid barrier (BCSFB) might contribute to age-related cognitive decline and neurodegenerative disease. We used the CPs from young (1-2 years), middle-aged (3-6 years) and old (7-10 years) sheep to explore effects of aging on various aspects of CP and BCSFB functions. Total protein in the cerebrospinal fluid (CSF) was significantly higher in old compared to young sheep and CSF secretion by the CP perfused in situ was significantly lower in both old and middle-aged when compared to young sheep, which correlated with reduced Na-22(+) uptake and efflux by the CP. Steady-state extractions of a low and medium size molecular weight extracellular space marker, 14 C-mannitol and 3 H-polyethylene glycol, respectively, were significantly higher in CPs from old compared to young animals; however, there was no significant difference in steady-state extraction of a high molecular weight marker, (125)l-bovine serum albumin. This indicates increased passive BCSFB permeability for small and medium sized molecules in old sheep. CP redox activity was significantly lower in the old animals as assessed by the MTT assay, however, there was no significant difference in ATP content and energy charge of the CP with age suggesting adequate baseline energy reserve capacity. These data indicate that normal aging processes alter protein content in the CSF, CSF secretion, integrity of the BCSFB and Na+ flux in the epithelial layer, which could impact on CSF homeostasis and turnover. (C) 2008 Elsevier Inc. All rights reserved.