Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C

Eric C. Bascuñan-Castillo, Robert P. Erickson, Christy M. Howison, Robert J. Hunter, Randall H. Heidenreich, Chad Hicks, Theodore P. Trouard, Robert J. Gillies

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is the result of deficient intracellular cholesterol movement. We investigated the effects of tamoxifen and vitamin E (D-alpha tocopherol) treatment on patterns of weight loss and motor function in the mouse model of Niemann-Pick C disease (Npc1-/- mice). Tamoxifen has multiple metabolic effects, including reducing oxidative damage, while vitamin E primarily has this property. Npc1-/- mice were identified and treatment was initiated at an approximate age of 21 days. Tamoxifen suspended in peanut oil was administered via intraperitoneal injection (weekly, at a dose calculated to deliver 0.023 μg/g/day). Vitamin E (25 IU) was administered orally via gavage once a week. Weight loss and Rota-Rod performance were analyzed by using Kaplan-Meyer survival curves. Tamoxifen treatment by itself significantly delayed weight loss (an endpoint of neurodegeneration) in male and female mice compared to untreated controls. Motor function was evaluated by performance on a Rota-Rod. Tamoxifen maintained Rota-Rod performance for about an extra week. Vitamin E treatment significantly delayed weight loss in females only. Rota-Rod performance was maintained slightly longer in mice treated with vitamin E. Simultaneous use of both treatments did not delay weight loss longer than tamoxifen-only treatment but had a greater effect than either treatment alone on Rota-Rod performance and demonstrated a significant positive effect on the early "learning curve" portion of the Rota-Rod evaluations. We found significant but relatively small improvements in rate of disease progression by treating Npc1-/- mice with tamoxifen and/or vitamin E. Some sex differences in response and an early improvement in Rota-Rod performance suggest areas for further study.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalJournal of Applied Genetics
Volume45
Issue number4
StatePublished - Dec 27 2004

Keywords

  • Mice
  • Neurodegeneration
  • Niemann-Pick C
  • Rota-Rod
  • Tamoxifen
  • Vitamin E

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C'. Together they form a unique fingerprint.

  • Cite this

    Bascuñan-Castillo, E. C., Erickson, R. P., Howison, C. M., Hunter, R. J., Heidenreich, R. H., Hicks, C., Trouard, T. P., & Gillies, R. J. (2004). Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C. Journal of Applied Genetics, 45(4), 461-467.