CREB Signaling Mediates Dose-Dependent Radiation Response in the Murine Hippocampus Two Years after Total Body Exposure

The
impact of low-dose ionizing radiation (IR) on the human brain
has recently attracted attention due to the increased use of IR for
diagnostic purposes. The aim of this study was to investigate low-dose
radiation response in the hippocampus. Female B6C3F1 mice were exposed
to total body irradiation with 0 (control), 0.063, 0.125, or 0.5 Gy.
Quantitative label-free proteomic analysis of the hippocampus was
performed after 24 months. CREB signaling and CREB-associated pathways
were affected at all doses. The lower doses (0.063 and 0.125 Gy) induced
the CREB pathway, whereas the exposure to 0.5 Gy deactivated CREB.
Similarly, the lowest dose (0.063 Gy) was anti-inflammatory, reducing
the number of activated microglia. In contrast, induction of activated
microglia and reactive astroglia was found at 0.5 Gy, suggesting increased
inflammation and astrogliosis, respectively. The apoptotic markers
BAX and cleaved CASP-3 and oxidative stress markers were increased
only at the highest dose. Since the activated CREB pathway plays a
central role in learning and memory, these data suggest neuroprotection
at the lowest dose (0.063 Gy) but neurodegeneration at 0.5 Gy. The
response to 0.5 Gy resembles alterations found in healthy aging and
thus may represent radiation-induced accelerated aging of the brain.