title: FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells.
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.
authors.affiliation: Department of Radiation Oncology, Weill Medical College of Cornell University, New York, NY 10065, USA. ams2009@nyp.org
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Stessin
authors.forename: Demirkan B
authors.initials: DB
authors.lastname: Gursel
authors.forename: Allie
authors.initials: A
authors.lastname: Schwartz
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Parashar
authors.forename: Fridon G
authors.initials: FG
authors.lastname: Kulidzhanov
authors.forename: Albert M
authors.initials: AM
authors.lastname: Sabbas
authors.forename: John
authors.initials: J
authors.lastname: Boockvar
authors.forename: Dattatreyudu
authors.initials: D
authors.lastname: Nori
authors.forename: A Gabriella
authors.initials: AG
authors.lastname: Wernicke
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016371:Cranial Irradiation / Q000009:adverse effects; D000068876:Fingolimod Hydrochloride; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011409:Propylene Glycols / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D011409:Propylene Glycols; D011837:Radiation-Protective Agents; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine