Abstract

The cellular form of the prion protein (PrPC) is a sialoglycoprotein widely expressed in the central nervous system (CNS) of mammalian species during neurodevelopment and in adulthood. The location of the protein in the CNS may play a role in the susceptibility of a species to fatal prion diseases, which are also known as the transmissible spongiform encephalopathies (TSEs). To date, little is known about PrPC distribution in marsupial mammals, for which no naturally occurring prion diseases have been reported. To extend our understanding of varying PrPC expression profiles in different mammals we carried out a detailed expression analysis of PrPC distribution along the neurodevelopment of the metatherian South American short-tailed opossum (Monodelphis domestica). We detected lower levels of PrPC in white matter fiber bundles of opossum CNS compared to mouse CNS. This result is consistent with a possible role for PrPC in the distinct neurodevelopment and neurocircuitry found in marsupials compared to other mammalian species.

Highlights

  • The cellular form of the prion protein (PrPC) is a cell-surface glycosylphosphatidylinositol-anchored glycopolypeptide abundantly expressed in the central nervous system (CNS), with expression levels varying among different cell types and brain regions [1]

  • The earliest expression of the protein in mammals has been observed in the hippocampus, thalamus and hypothalamus and the highest levels of PrPC expression have been noted in specific white matter fiber tracts [6]

  • To compare OpPrP and MoPrP distribution in CNS, we examined the expression of PrPC in postnatal 30-day-old (P30) mice – which resemble young adult Op in the overall development – under the same experimental conditions

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Summary

Introduction

The cellular form of the prion protein (PrPC) is a cell-surface glycosylphosphatidylinositol-anchored glycopolypeptide abundantly expressed in the central nervous system (CNS), with expression levels varying among different cell types and brain regions [1]. The distribution pattern of PrPC has already been investigated in deep detail in the CNS of several placental mammalian organisms, including mouse (Mo) [2,3,4,5,6], hamster [7], cattle [8], sheep [9] and primates [10,11]. The earliest expression of the protein in mammals has been observed in the hippocampus, thalamus and hypothalamus and the highest levels of PrPC expression have been noted in specific white matter fiber tracts [6]. The octapeptide-repeat region is able to coordinate the binding of copper ions, implicating a possible role of PrPC in copper homeostasis [16]

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