56 Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo

Nathan A. Decarolis, Phillip D. Rivera, Francisca Ahn, Wellington Z. Amaral, Junie A. Leblanc, Shveta Malhotra, Hung Ying Shih, David Petrik, Neal R. Melvin, Benjamin P C Chen, Amelia J. Eisch

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreER T2 /R26R:YFP mice, respectively). Mice were subjected to 56 Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24 h), intermediate (7 d), and/or long time points (2-3 mo) post-irradiation. 56 Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56 Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56 Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56 Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56 Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support the regenerative capacity of the adult SGZ after HZE particle exposure and encourage additional inquiry into the relationship between radial glia stem cells and cognitive function after HZE particle exposure.

Original languageEnglish (US)
Pages (from-to)70-79
Number of pages10
JournalLife Sciences in Space Research
Volume2
DOIs
StatePublished - Jan 1 2014

Keywords

  • Adult neurogenesis
  • BrdU
  • Galactic cosmic radiation
  • Recovery
  • Subgranular zone
  • Transgenic mice

ASJC Scopus subject areas

  • Radiation
  • Ecology
  • Astronomy and Astrophysics
  • Agricultural and Biological Sciences (miscellaneous)
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of '<sup>56</sup> Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo'. Together they form a unique fingerprint.

Cite this