TY - JOUR
T1 - 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
AU - Decarolis, Nathan A.
AU - Rivera, Phillip D.
AU - Ahn, Francisca
AU - Amaral, Wellington Z.
AU - Leblanc, Junie A.
AU - Malhotra, Shveta
AU - Shih, Hung Ying
AU - Petrik, David
AU - Melvin, Neal R.
AU - Chen, Benjamin P C
AU - Eisch, Amelia J.
N1 - Funding Information:
This work was supported by grants from the National Aeronautics and Space Administration ( BPCC/AJE NNX07AP84G , AJE/BPCC NNX12AB55G ) and National Institutes of Health ( R01 DA016765 and K02 DA023555 to AJE; F31 NS064632 to NAD and T32 DA07290 to PDR/NAD/AJE). The authors would like to thank Adam Carlton, Mara Cole, Laure Farnbauch, Harry Han, Irene Masiulis, Maxwell Mechanic, Devon Richardson, Sanghee Yun, and Shichuan Zhang for their helpful contributions to these experiments.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Adult neurogenesis
KW - BrdU
KW - Galactic cosmic radiation
KW - Recovery
KW - Subgranular zone
KW - Transgenic mice
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U2 - 10.1016/j.lssr.2014.06.004
DO - 10.1016/j.lssr.2014.06.004
M3 - Article
C2 - 25170435
AN - SCOPUS:84904859894
SN - 2214-5524
VL - 2
SP - 70
EP - 79
JO - Life Sciences in Space Research
JF - Life Sciences in Space Research
ER -