Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus

Benvegnu S, Roncaglia P, Agostini F, Casalone C, Corona C, Gustincich S, Legname G. Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus. Physiol Genomics 43: 711-725, 2011. First published March 15, 2011; doi:10.1152/physiolgenomics.00205.2010.-The conversion of the cellular prion protein (PrPC) to an abnormal and protease-resistant isoform is the key event in prion diseases. Mice lacking PrPC are resistant to prion infection, and downregulation of PrPC during prion infection prevents neuronal loss and the progression to clinical disease. These results are suggestive of the potential beneficial effect of silencing PrPC during prion diseases. However, the silencing of a protein that is widely expressed throughout the central nervous system could be detrimental to brain homeostasis. The physiological role of PrPC remains still unclear, but several putative functions (e. g., neuronal development and maintenance) have been proposed. To assess the influence of PrPC on gene expression profile in the mouse brain, we undertook a microarray analysis by using RNA isolated from the hippocampus at two different developmental stages: newborn (4.5-day-old) and adult (3-mo-old) mice, both from wild-type and Prnp(0/0) animals. Comparing the different datasets allowed us to identify commonly co-regulated genes and uniquely deregulated genes during postnatal development. The absence of PrPC affected several biological pathways, the most representative being cell signaling, cell-cell communication and transduction processes, calcium homeostasis, nervous system development, synaptic transmission, and cell adhesion. However, there was only a moderate alteration of the gene expression profile in our animal models. PrPC deficiency did not lead to a dramatic alteration of gene expression profile and produced moderately altered gene expression levels from young to adult animals. Thus, our results may provide additional support to silencing endogenous PrPC levels as therapeutic approach to prion diseases.