Transcriptome Differences Between the Frontal Cortex and Hippocampus of Wild-Type and Humanized Presenilin-1 Transgenic Mice

Abstract

Objective 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 ΔE9 hPS1 mutant mice. Methods Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and ΔE9 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. Results 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 ΔE9 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 ΔE9 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. Conclusions Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology. 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 ΔE9 hPS1 mutant mice. Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and ΔE9 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 ΔE9 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 ΔE9 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.