Effects of folate on the brain gene expression of Tg2576 transgenic mice treated with Alzheimer drug memantine: a pilot study using cDNA microarray profiling

Abstract

Using Tg2576 transgenic mice that produce endogenous beta‐amyloid (Aβ) protein in brain, we have previously reported that high dose of folic acid supplemented to Alzheimer drug memantine (MT)‐treated AD mice significantly improved the neuronal functional performance on Morris water maze test. To further study effects of folate on the brain gene expression profile of MT‐treated transgenic mice, a total of 6 Aβ mice brains (3 from MT mice and 3 from folate+MT mice) were analyzed by cDNA microarrays. Total RNA isolation, cDNA synthesis and cy3 and 5 dye labeling were performed using standard protocols. The labeled samples were hybridized to Agilent Whole Mouse Genome Oligo Microarray containing 41,000+ annotated genes and transcripts. Expression data were analyzed using GeneSpring GX 10. Only genes with net expression changes of > 2‐fold occurring among 20‐100th percentile of expression levels in each hybridized arrays were considered for further analysis. Compared to MT‐treated Aβ mice brains, folate+MT brains showed a generalized up‐regulation of 72 brain gene transcriptions involving in neurogenesis, memory, action potential production, neurotransmitter receptors, vasodilation, and immune modulation. Down regulations were only found in 9 transcripts. Validation of gene expressions by real‐time PCR and the significance of modulated expression profiles by folate will be further discussed.