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

► FTY720 increases the viability and neurogenicity of irradiated neural stem cells. ► FTY720 does not increase the viability of irradiated glioma or breast cancer cells. ► Potential use of FTY720 as neuroprotector during cranial irradiation is suggested. Cranial irradiation is an effective treatment...

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Bibliographic Details
Published in:Neuroscience letters 2012-05, Vol.516 (2), p.253-258
Main Authors: Stessin, Alexander M., Gursel, Demirkan B., Schwartz, Allie, Parashar, Bhupesh, Kulidzhanov, Fridon G., Sabbas, Albert M., Boockvar, John, Nori, Dattatreyudu, Wernicke, A. Gabriella
Format: Article
Language:English
Subjects:
Cell Differentiation - drug effects
Cell Line
Cell Survival - drug effects
Cranial Irradiation - adverse effects
End results
External beam radiotherapy
Fingolimod
Fingolimod Hydrochloride
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - metabolism
Humans
Immunohistochemistry
Neural stem cells
Neural Stem Cells - cytology
Neural Stem Cells - drug effects
Neural Stem Cells - metabolism
Neuroprotective Agents - pharmacology
Propylene Glycols - pharmacology
Radiation sensitivity
Radiation-Protective Agents - pharmacology
Receptors, Lysosphingolipid - metabolism
Sphingosine - analogs & derivatives
Sphingosine - pharmacology
Surveillance epidemiology
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Summary:► FTY720 increases the viability and neurogenicity of irradiated neural stem cells. ► FTY720 does not increase the viability of irradiated glioma or breast cancer cells. ► Potential use of FTY720 as neuroprotector during cranial irradiation is suggested. 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.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2012.04.004