Expression of vascular endothelial growth factor (VEGF) mRNA, VEGF receptor 2 (Flk-1) mRNA, and of VEGF co-receptor neuropilin (Nrp)-1 mRNA in brain tissue of aging Tg2576 mice by in situ hybridization

Abstract

Vascular endothelial growth factor (VEGF) has been characterized as a heparin binding angiogenic growth factor displaying high specificity for endothelial cells. It is profoundly accumulated and co-localized with amyloid beta (Aβ) plaques in the brain of Alzheimer's disease patients. In order to examine the effect of Aβ plaques on the expression level of VEGF mRNA and its receptors, brain tissue of both transgenic Tg2576 and wild type mice at ages ranging from 13 to 22 months was subjected to in situ hybridization followed by densitometric assessment using computer-assisted image analysis. Strong expression of VEGF mRNA, fetal liver kinase (Flk)-1 mRNA, and neuropilin (Nrp)-1 mRNA in the piriform, entorhinal, somatosensory, frontal cortex and hippocampal formation of both transgenic and non-transgenic mice brain was detected. Developmentally, only expression of VEGF mRNA was increased with age in the entorhinal, and somatosensory cortex of wild type mice. In 20-month-old transgenic Tg2576 mice, up-regulation of VEGF mRNA, Flk-1 mRNA, and Nrp-1 mRNA transcripts was observed in the entorhinal cortex compared to age-matched wild type mice. Our data suggest up-regulation of VEGF mRNA, Flk-1 mRNA and Nrp-1 mRNA, at least in the entorhinal cortex at ages when Aβ deposition in Tg2576 is typically increasing.

Keywords: Beta amyloid plaques; Flk-1 mRNA; Nrp-1 mRNA; Transgenic mouse brain; VEGF mRNA.