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

Hermann M. Schätzl, L. László, David M. Holtzman, Jörg Tatzelt, Stephen J. Dearmond, Richard I. Weiner, William C. Mobley, Stanley B. Prusiner

Research output: Contribution to journalArticle

224 Citations (Scopus)

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, J. J. 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 triad 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.

Original languageEnglish
Pages (from-to)8821-8831
Number of pages11
JournalJournal of Virology
Volume71
Issue number11
Publication statusPublished - Nov 1997

Fingerprint

Scrapie
scrapie
Prions
prions
apoptosis
neurons
cell lines
Apoptosis
Cell Line
cells
nerve growth factor
viability
neuropathology
Neurons
Nerve Growth Factor Receptor
Prion Diseases
prion diseases
mice
Nerve Growth Factor
gonadotropin-releasing hormone

ASJC Scopus subject areas

  • Immunology

Cite this

Schätzl, H. M., László, L., Holtzman, D. M., Tatzelt, J., Dearmond, S. J., Weiner, R. I., ... Prusiner, S. B. (1997). A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. Journal of Virology, 71(11), 8821-8831.

A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. / Schätzl, Hermann M.; László, L.; Holtzman, David M.; Tatzelt, Jörg; Dearmond, Stephen J.; Weiner, Richard I.; Mobley, William C.; Prusiner, Stanley B.

In: Journal of Virology, Vol. 71, No. 11, 11.1997, p. 8821-8831.

Research output: Contribution to journalArticle

Schätzl, HM, László, L, Holtzman, DM, Tatzelt, J, Dearmond, SJ, Weiner, RI, Mobley, WC & Prusiner, SB 1997, 'A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis', Journal of Virology, vol. 71, no. 11, pp. 8821-8831.
Schätzl HM, László L, Holtzman DM, Tatzelt J, Dearmond SJ, Weiner RI et al. A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. Journal of Virology. 1997 Nov;71(11):8821-8831.
Schätzl, Hermann M. ; László, L. ; Holtzman, David M. ; Tatzelt, Jörg ; Dearmond, Stephen J. ; Weiner, Richard I. ; Mobley, William C. ; Prusiner, Stanley B. / A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. In: Journal of Virology. 1997 ; Vol. 71, No. 11. pp. 8821-8831.
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