FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells

Alexander M. Stessin*, Demirkan B. Gursel, Allie Schwartz, Bhupesh Parashar, Fridon G. Kulidzhanov, Albert M. Sabbas, John Boockvar, Dattatreyudu Nori, A. Gabriella Wernicke

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Cranial irradiation is an effective treatment modality for both primary and metastatic brain tumors, yet it induces cognitive decline in a substantial number of patients. At present, there are no established methods for neuroprotection. Recent investigations have revealed a link between radiation-induced cognitive dysfunction and the loss of neural precursor cells in the hippocampus. Hence, identifying pharmacological agents, capable of protecting this cell population, is of interest. FTY720 (fingolimod), an FDA-approved oral drug for the treatment of multiple sclerosis, has been shown to promote the survival and differentiation of neural progenitors, as well as remyelination and repair after brain injury. In this study, we show that FTY720, used at nanomolar concentrations, is capable of increasing the viability and neurogenicity of irradiated neural stem cells from the hippocampus. In contrast, it does not provide radioprotection in a human breast cancer cell line and two glioma cell lines. These results suggest a potential therapeutic role for FTY720 as a neuroprotector during cranial irradiation. Further preclinical studies are warranted to evaluate this possibility.

Original languageEnglish (US)
Pages (from-to)253-258
Number of pages6
JournalNeuroscience Letters
Volume516
Issue number2
DOIs
StatePublished - May 16 2012

Keywords

  • End results
  • External beam radiotherapy
  • Fingolimod
  • Neural stem cells
  • Radiation sensitivity
  • Surveillance epidemiology

ASJC Scopus subject areas

  • Neuroscience(all)

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    Stessin, A. M., Gursel, D. B., Schwartz, A., Parashar, B., Kulidzhanov, F. G., Sabbas, A. M., Boockvar, J., Nori, D., & Wernicke, A. G. (2012). FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells. Neuroscience Letters, 516(2), 253-258. https://doi.org/10.1016/j.neulet.2012.04.004