Abstract
Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8–15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests.
Highlights
Exposure to ionizing radiation is known to induce a plethora of adverse health consequences, with the severity of the effects greatly depending on the dose (Williams and Fletcher, 2010)
Taking the three main categories of swim strategies into account, we found that control animals increasingly used spatial search strategies, assumed to be the most efficient and cognitively demanding strategies (Lo et al, 2013, 2014)
Epidemiological research substantiated in utero radiation-induced late neurological deficits and provided evidence that these defects can be caused by exposure to relatively low doses, i.e. around 0.10 Gy (Otake et al, 1996)
Summary
Exposure to ionizing radiation is known to induce a plethora of adverse health consequences, with the severity of the effects greatly depending on the dose (Williams and Fletcher, 2010). Aberrant open field and radial arm maze performance has been found in mice prenatally exposed to 0.30 and 0.35 Gy, but not in those exposed to 0.25 Gy (Baskar and Devi, 2000; Hossain and Uma Devi, 2000). In light of this discrepancy, the consequences of in utero radiation exposure to low doses
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