Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus.
Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus.
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DOI：
10.1186/1743-8454-6-4
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发表时间：
2009-05-26
影响因子：
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通讯作者：
McAllister JP 2nd
中科院分区：
文献类型：
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作者：
Deren KE;Forsyth J;Abdullah O;Hsu EW;Klinge PM;Silverberg GD;Johanson CE;McAllister JP 2nd
先前对衰老动物的研究表明，脑积水期间，β-淀粉样蛋白 (Aβ) 会积累，其转运蛋白、低密度脂蛋白受体相关蛋白 1 (LRP-1) 和晚期糖基化终末产物 (RAGE) 受体也会受损。此外，在人类常压脑积水 (NPH) 和阿尔茨海默病 (AD) 病例中发现了星形胶质细胞和 Aβ 之间的相关性。由于脑积水在儿童中经常发生，我们评估了新生儿脑积水动物中 Aβ 及其转运蛋白的表达和反应性星形细胞增多症。新生大鼠在出生后第一天通过脑池内注射高岭土诱发脑积水，并在三周内出现严重的脑室扩大。在使用高岭土后第 10 天和第 21 天进行 MRI 以记录脑室扩大情况。在高岭土后第 21 天处死动物。为了进行与年龄相关的比较，使用了先前研究中在 6 个月或 12 个月大的成年动物中诱发脑积水时的组织。对组织进行免疫组织化学处理，以可视化 LRP-1、RAGE、Aβ 和胶质纤维酸性蛋白 (GFAP)，并使用定量实时逆转录酶聚合酶链反应 (qRT-PCR) 来量化 LRP-1、RAGE 和 GFAP 的表达。将高岭土后 21 天的新生脑积水动物与成年（6-12 个月大）脑积水动物进行比较时，免疫组织化学显示 Aβ、RAGE 和 LRP-1 水平在年轻动物中显着较低；相比之下，年轻和年老脑积水动物的 GFAP 水平均升高。当新生脑积水动物与年龄匹配的对照组进行比较时，qRT-PCR 显示 Aβ、LRP-1 和 RAGE 没有显着变化。然而，免疫组织化学显示单个蛋白质的增加或减少非常小。此外，qRT-PCR 表明 GFAP 具有统计学上的显着增加。与患有脑积水的成年大鼠相比，患有或不患有脑积水的新生大鼠 Aβ 及其转运蛋白的表达较低。对照组和脑积水新生动物之间的 Aβ 及其转运蛋白没有观察到统计学差异。
Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus. Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP. When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP. Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.