Unger Travis, Korade Zeljka, Lazarov Orly, Terrano David, Schor Nina F, Sisodia Sangram S, Mirnics Károly
Department of Psychiatry, University of Pittsburgh School of Medicine, E1453 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Am J Geriatr Psychiatry. 2005 Dec;13(12):1041-51. doi: 10.1176/appi.ajgp.13.12.1041.
The authors investigated the differences between the frontal cortical (Fc) and hippocampal (Hc) transcriptomes of wild type (wt mPS1), humanized presenilin-1 (PS1 [wt hPS1]) and Alzheimer-disease (AD)-linked DeltaE9 hPS1 mutant mice.
Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and DeltaE9 hPS1 mutant mice. Whereas these studies analyzed the commonalities of gene expression patterns and commonly-regulated genes across the two brain areas and across the animal models, the current study focused on the gene-expression differences across Fc and Hc, two critical AD-affected brain regions.
The data revealed that in the wild-type mice, there are significant transcriptome differences between the Fc and the Hc tissue, and these expression differences are maintained in humanized transgenic mice carrying the wt hPS1 gene or DeltaE9 hPS1 mutation. Also, they provide evidence that a subset of genes show disturbed regional Fc-Hc gene-expression ratios in the transgenic mice carrying the DeltaE9 hPS1 mutation. Some of these genes, including stearoyl-Coenzyme A desaturase-2 (Scd2) and Prostaglandin D2 synthase (Ptgds), have been previously implicated in the pathology of AD.
Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology.
作者研究了野生型（wt mPS1）、人源化早老素-1（PS1 [wt hPS1]）和与阿尔茨海默病（AD）相关的DeltaE9 hPS1突变小鼠的额叶皮质（Fc）和海马体（Hc）转录组之间的差异。
他们最近使用高密度寡核苷酸阵列对wt mPS1、wt hPS1和DeltaE9 hPS1突变小鼠进行了转录组分析。虽然这些研究分析了两个脑区以及不同动物模型之间基因表达模式和共同调控基因的共性，但当前研究聚焦于Fc和Hc这两个受AD影响的关键脑区之间的基因表达差异。
数据显示，在野生型小鼠中，Fc和Hc组织之间存在显著的转录组差异，并且这些表达差异在携带wt hPS1基因或DeltaE9 hPS1突变的人源化转基因小鼠中得以维持。此外，他们提供的证据表明，在携带DeltaE9 hPS1突变的转基因小鼠中，一部分基因的区域Fc - Hc基因表达比率受到干扰。其中一些基因，包括硬脂酰辅酶A去饱和酶-2（Scd2）和前列腺素D2合酶（Ptgds），先前已被认为与AD的病理学有关。
数据表明，皮质区域之间受干扰的基因表达比率可能是大脑生理改变中的一个重要事件。
