Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation

Bertrand P. Tseng, Erich Giedzinski, Atefeh Izadi, Tatiana Suarez, Mary L. Lan, Katherine K. Tran, Munjal M. Acharya, Gregory A. Nelson, Jacob Raber, Vipan K. Parihar, Charles L. Limoli

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Aims: Redox homeostasis is critical in regulating the fate and function of multipotent cells in the central nervous system (CNS). Here, we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment. Results: Low doses (<1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (<1 week) irradiation, increased levels of reactive oxygen and nitrogen species were generally dose responsive, but were less dependent on dose weeks to months thereafter. Exposure to ion fluences resulting in less than one ion traversal per cell was sufficient to elicit radiation-induced oxidative stress. Whole body irradiation triggered a compensatory response in the rodent brain that led to a significant increase in antioxidant capacity 2 weeks following exposure, before returning to background levels at week 4. Low dose irradiation was also found to significantly impair novel object recognition in mice 2 and 12 weeks following irradiation. Innovation: Data provide evidence that acute exposure of neural stem cells and the CNS to very low doses and fluences of charged particles can elicit a persisting oxidative stress lasting weeks to months that is associated with impaired cognition. Conclusions: Exposure to low doses of charged particles causes a persistent oxidative stress and cognitive impairment over protracted times. Data suggest that astronauts subjected to space radiation may develop a heightened risk for mission critical performance decrements in space, along with a risk of developing long-term neurocognitive sequelae. Antioxid.

Original languageEnglish (US)
Pages (from-to)1410-1422
Number of pages13
JournalAntioxidants and Redox Signaling
Volume20
Issue number9
DOIs
StatePublished - Mar 20 2014

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Tseng, B. P., Giedzinski, E., Izadi, A., Suarez, T., Lan, M. L., Tran, K. K., Acharya, M. M., Nelson, G. A., Raber, J., Parihar, V. K., & Limoli, C. L. (2014). Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation. Antioxidants and Redox Signaling, 20(9), 1410-1422. https://doi.org/10.1089/ars.2012.5134