Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months.
Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months.
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DOI：
10.1186/2045-8118-9-3
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发表时间：
2012-01-23
影响因子：
7.3
通讯作者：
Silverberg GD
中科院分区：
文献类型：
--
作者：
Chiu C;Miller MC;Caralopoulos IN;Worden MS;Brinker T;Gordon ZN;Johanson CE;Silverberg GD
淀粉样蛋白在脑实质中的积累是阿尔茨海默病（AD）的标志，并且在正常衰老中可见。脑脊液（CSF）动力学的改变也与正常衰老和AD相关。本研究分析了衰老大鼠大脑中与淀粉样β肽（Aβ）积聚相关的CSF体积、产量和周转率。研究了3、12、20和30个月龄的老化Fischer 344/Brown-Norway杂交大鼠。通过在人工CSF中用蓝色葡聚糖进行脑室-脑池灌注来测量CSF产生;通过MRI测量CSF体积;并且通过将CSF产生速率除以CSF空间的体积来测量CSF转换速率。ELISA法测定大脑皮层和海马Aβ40和Aβ42的含量。随着年龄的增长，颅内CSF总量呈显著线性增加：3-20个月（p < 0.01）; 3-30个月（p < 0.001）。CSF生成率从3-12个月增加（p < 0.01），从12-30个月降低（p < 0.05）。CSF周转率显示从3个月（9.40天-1）开始增加至12个月（11.30天-1），然后减少至20个月（10.23天-1）和30个月（6.62天-1）。脑中Aβ40和Aβ42浓度从3-30个月增加（p < 0.001）。30个月时，Aβ42和Aβ40浓度均接近稳态水平。在幼龄大鼠中，CSF转换与Aβ脑浓度之间无相关性。12个月后，随着脑Aβ继续蓄积，CSF周转率降低。CSF周转率的降低可能是影响年龄相关的脑淀粉样蛋白积累的几种清除途径改变之一。
Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer's disease (AD) and is seen in normal aging. Alterations in cerebrospinal fluid (CSF) dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Aβ) accumulation in the aging rat brain. Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Aβ40 and Aβ42 concentrations in the cortex and hippocampus were measured by ELISA. There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p < 0.01); 3-30 months (p < 0.001). CSF production rate increased from 3-12 months (p < 0.01) and decreased from 12-30 months (p < 0.05). CSF turnover showed an initial increase from 3 months (9.40 day-1) to 12 months (11.30 day-1) and then a decrease to 20 months (10.23 day-1) and 30 months (6.62 day-1). Aβ40 and Aβ42 concentrations in brain increased from 3-30 months (p < 0.001). Both Aβ42 and Aβ40 concentrations approached a steady state level by 30 months. In young rats there is no correlation between CSF turnover and Aβ brain concentrations. After 12 months, CSF turnover decreases as brain Aβ continues to accumulate. This decrease in CSF turnover rate may be one of several clearance pathway alterations that influence age-related accumulation of brain amyloid.