载脂蛋白D信使核糖核酸在PDAPP转基因小鼠中的表达升高。

Apolipoprotein D mRNA expression is elevated in PDAPP transgenic mice.

作者信息

Thomas E A, Sautkulis L N, Criado J R, Games D, Sutcliffe J G

机构信息

Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.

出版信息

J Neurochem. 2001 Dec;79(5):1059-64. doi: 10.1046/j.1471-4159.2001.00654.x.

DOI:10.1046/j.1471-4159.2001.00654.x

PMID:11739619

Abstract

Apolipoprotein D (apoD) expression is known to be elevated in select regions of rodent and human brain in association with different types of CNS pathology. To investigate a potential role for apoD in the neuropathology of Alzheimer's disease, we have measured apoD mRNA expression in transgenic mice expressing mutated human amyloid precursor protein under control of platelet-derived growth factor promoter (PDAPP mice). In situ hybridization analysis revealed increased apoD mRNA expression in brains of aged (26 months) PDAPP transgenic mice compared to aged littermate controls. These increases were most prominent in the hippocampal fimbria, corpus callosum and other white matter tracts. No substantial increases in expression were observed in white matter regions in young (6 months) PDAPP transgenic mice compared to young controls. Comparison between aged and young control mice revealed increased apoD expression in similar white matter regions of the aged animals. These findings suggest that, although increases in apoD expression are a normal feature of brain aging, super-increases may represent a glial cell compensatory response to beta-amyloid deposition in Alzheimer's disease.

摘要

已知载脂蛋白D（apoD）在啮齿动物和人类大脑的特定区域表达升高，与不同类型的中枢神经系统病理学相关。为了研究apoD在阿尔茨海默病神经病理学中的潜在作用，我们测量了在血小板衍生生长因子启动子控制下表达突变型人类淀粉样前体蛋白的转基因小鼠（PDAPP小鼠）中apoD mRNA的表达。原位杂交分析显示，与同龄同窝对照相比，老年（26个月）PDAPP转基因小鼠大脑中apoD mRNA表达增加。这些增加在海马伞、胼胝体和其他白质束中最为明显。与年轻对照相比，年轻（6个月）PDAPP转基因小鼠的白质区域未观察到表达的实质性增加。老年和年轻对照小鼠之间的比较显示，老年动物类似白质区域中apoD表达增加。这些发现表明，虽然apoD表达增加是大脑衰老的正常特征，但超量增加可能代表了阿尔茨海默病中胶质细胞对β-淀粉样蛋白沉积的代偿反应。