Subcellular distribution of the prion protein in sickness and in health.

The cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein that is most abundant in the central nervous system. It is thought to play a role in many cellular processes, including neuroprotection, but may also contribute to Alzheimer's disease and some cancers. However, it is best known for its central role in the prion diseases, such as Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE), and scrapie.

Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs.

Mammalian prions refold host glycosylphosphatidylinositol-anchored PrP(C) into β-sheet-rich PrP(Sc). PrP(Sc) is rapidly truncated into a C-terminal PrP27-30 core that is stable for days in endolysosomes. The nature of cell-associated prions, their attachment to membranes and rafts, and their subcellular locations are poorly understood; live prion visualization has not previously been achieved.

Plasma membrane invaginations containing clusters of full-length PrPSc are an early form of prion-associated neuropathology in vivo.

During prion disease, cellular prion protein (PrP(C)) is refolded into a pathogenic isoform (PrP(Sc)) that accumulates in the central nervous system and causes neurodegeneration and death. We used immunofluorescence, quantitative cryo-immunogold EM, and tomography to detect nascent, full-length PrP(Sc) in the hippocampus of prion-infected mice from early preclinical disease stages onward. Comparison of uninfected and infected brains showed that sites containing full-length PrP(Sc) could be recognized in the neuropil by bright spots and streaks of immunofluorescence on semi-thin (200-nm) sections, and by clusters of cryo-immunogold EM labeling.

Prion uptake in the gut: identification of the first uptake and replication sites.

After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice.

Cryo-immunogold electron microscopy for prions: toward identification of a conversion site.

Prion diseases are caused by accumulation of an abnormally folded isoform (PrP(Sc)) of the cellular prion protein (PrP(C)). The subcellular distribution of PrP(Sc) and the site of its formation in brain are still unclear. We performed quantitative cryo-immunogold electron microscopy on hippocampal sections from mice infected with the Rocky Mountain Laboratory strain of prions.

Androgen receptors in the embryonic zebra finch hindbrain suggest a function for maternal androgens in perihatching survival.

Bird embryos are exposed to maternal androgens deposited in the egg, but the role of these hormones in embryonic development and hatchling survival is unclear. To identify possible target organs, we used in situ hybridization to study the distribution of androgen receptor (AR) RNA in the developing zebra finch brain. The first brain expression domain of AR mRNA is in the hindbrain.