A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis

Author:

Schätzl H M1,Laszlo L1,Holtzman D M1,Tatzelt J1,DeArmond S J1,Weiner R I1,Mobley W C1,Prusiner S B1

Affiliation:

1. Department of Neurology, University of California, San Francisco 94143, USA.

Abstract

Neuronal death and vacuolation are characteristics of the CNS degeneration found in prion diseases. Relatively few cultured cell lines have been identified that can be persistently infected with scrapie prions, and none of these cells show cytopathologic changes reminiscent of prion neuropathology. The differentiated neuronal cell line GT1, established from gonadotropin hormone releasing-hormone neurons immortalized by genetically targeted tumorigenesis in transgenic mice (P. L. Mellon, JJ. Windle, P. C. Goldsmith, C. A. Padula, J. L. Roberts, and R. I. Weiner, Neuron 5:1-10, 1990), was examined for its ability to support prion formation. We found that GT1 cells could be persistently infected with mouse RML prions and that conditioned medium from infected cells could transfer prions to uninfected cells. In many but not all experiments, a subpopulation of cells showed reduced viability, morphological signs of neurodegeneration and vacuolation, and features of apoptosis. Subclones of GT1 cells that were stably transfected with the trk4 gene encoding the high-affinity nerve growth factor (NGF) receptor (GT1-trk) could also be persistently infected. NGF increased the viability of the scrapie-infected GT1-trk cells and reduced the morphological and biochemical signs of vacuolation and apoptosis. GT1 cells represent a novel system for studying the molecular mechanisms underlying prion infectivity and subsequent neurodegenerative changes.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference64 articles.

1. Programmed cell death: the paths to suicide;Altman J.;Trends Neurosci.,1992

2. Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein;Arrigo A. P.;Mol. Cell. Biol.,1988

3. Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells;Borchelt D. R.;J. Cell Biol.,1990

4. NGF retards apoptosis in chick embryo bursal cell in vitro;Bracchi-Laudiero L.;Differentiation,1993

5. Mouse cortical cells lacking cellular PrP survive in culture with a neurotoxic PrP fragment;Brown D. R.;Neuroreport,1994

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