Radiation and Environmental Biophysics

, Volume 46, Issue 2, pp 167–172

Redox changes induced in hippocampal precursor cells by heavy ion irradiation

  • C. L. Limoli
  • E. Giedzinski
  • J. Baure
  • R. Rola
  • J. R. Fike
Proceedings of the 4th IWSRR

DOI: 10.1007/s00411-006-0077-9

Cite this article as:
Limoli, C.L., Giedzinski, E., Baure, J. et al. Radiat Environ Biophys (2007) 46: 167. doi:10.1007/s00411-006-0077-9

Abstract

Hippocampal precursors retain the capacity to proliferate and differentiate throughout life, and their progeny, immature neurons, can undergo neurogenesis, a process believed to be important in maintaining the cognitive health of an organism. A variety of stresses including irradiation have been shown to deplete neural precursor cells, an effect that inhibits neurogenesis and is associated with the onset of cognitive impairments. Our past work has shown that neural precursor cells exposed to X-rays or protons exhibit a prolonged increase in oxidative stress, a factor we hypothesize to be critical in regulating the function of these cells after irradiation and other stresses. Here we report that irradiation of hippocampal precursor cells with high-linear energy transfer (LET) 1 GeV/nucleon 56Fe ions leads to significantly higher levels of oxidative stress when compared to lower LET radiations (X-rays, protons). Irradiation with 1 Gy of 56Fe ions elicits twofold to fivefold higher levels of reactive oxygen species (ROS) compared to unirradiated controls, and at lower doses (≤1 Gy) neural precursors exhibit a linear dose response 6 h after heavy ion exposure. The use of the antioxidant lipoic acid (LA) was able to reduce ROS levels below background levels when added before or after 56Fe ion irradiation. These results conclusively show that low doses of 56Fe ions can elicit significant levels of oxidative stress in neural precursor cells. Given the prevalence of heavy ions in space and the duration of interplanetary travel, these data suggest that astronauts are at risk for developing cognitive decrements. However, our results also indicate that antioxidants delivered before as radioprotective agents or after as mitigating agents hold promise as effective countermeasures for ameliorating certain adverse effects of heavy ion exposure to the CNS.

Abbreviations

CM-H2DCFDA

5-(and-6)-Chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate

FACS

Fluorescent activated cell sorting

SGZ

Subgranular zone of the dentate gyrus

ROS

Reactive oxygen species

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • C. L. Limoli
    • 1
  • E. Giedzinski
    • 1
  • J. Baure
    • 2
  • R. Rola
    • 2
  • J. R. Fike
    • 2
  1. 1.Department of Radiation OncologyUniversity of California IrvineIrvineUSA
  2. 2.Department of Neurological SurgeryUniversity of CaliforniaSan FranciscoUSA