PrPC glycoform heterogeneity as a function of brain region: Implications for selective targeting of neurons by prion strains

We recently found that deletion of the Asn-linked carbohydrate (CHO) at residue 197 of Syrian hamster (SHa) PrPc while retaining the CHO at Asn 181 has a profound effect on which population of neurons are targeted for conversion of SHaPrP(c) to SHaPrP(Sc) in transgenic (Tg) mice inoculated with scrapie prions. We hypothesized that selective targeting of neuronal populations is determined by cell-specific differences in the affinity of an infecting PrPSc (prion) for PrPc and that the affinity might be modulated by nerve cell-specific differences in PrPc glycosylation. Here we tested this hypothesis by assessing whether or not each brain region in Syrian hamsters synthesizes different PrPc glycoforms, as inferred from 2D-gel electrophoresis. Reproducible differences in the number and isoelectric point of PrPc charge isomers were found as a function of brain region. The results of this study support the hypothesis that the PrPSc accumulation and the vacuolation pattern phenotypes in the brain are governed by neuron-specific differences in PrPc glycoforms.