Title: A multidisciplinary approach unravels early and persistent effects of X-ray exposure at the onset of prenatal neurogenesis
Authors: Verreet, Tine
Quintens, Roel
Van Dam, Debby
Verslegers, Mieke
Tanori, Mirella
Casciati, Arianna
Neefs, Mieke
Leysen, Liselotte
Michaux, Arlette
Janssen, Ann
D'Agostino, Emiliano
Vande Velde, Greetje
Baatout, Sarah
Moons, Lieve
Pazzaglia, Simonetta
Saran, Anna
Himmelreich, Uwe
De Deyn, Peter Paul
Benotmane, Mohammed Abderrafi # ×
Issue Date: 9-Jan-2015
Publisher: Springer New York LLC
Series Title: Journal of Neurodevelopmental Disorders vol:7 issue:3 pages:1-21
Abstract: Background

In humans, in utero exposure to ionising radiation results in an increased prevalence of neurological aberrations, such as small head size, mental retardation and decreased IQ levels. Yet, the association between early damaging events and long-term neuronal anomalies remains largely elusive.


Mice were exposed to different X-ray doses, ranging between 0.0 and 1.0 Gy, at embryonic days (E) 10, 11 or 12 and subjected to behavioural tests at 12 weeks of age. Underlying mechanisms of irradiation at E11 were further unravelled using magnetic resonance imaging (MRI) and spectroscopy, diffusion tensor imaging, gene expression profiling, histology and immunohistochemistry.


Irradiation at the onset of neurogenesis elicited behavioural changes in young adult mice, dependent on the timing of exposure. As locomotor behaviour and hippocampal-dependent spatial learning and memory were most particularly affected after irradiation at E11 with 1.0 Gy, this condition was used for further mechanistic analyses, focusing on the cerebral cortex and hippocampus. A classical p53-mediated apoptotic response was found shortly after exposure. Strikingly, in the neocortex, the majority of apoptotic and microglial cells were residing in the outer layer at 24 h after irradiation, suggesting cell death occurrence in differentiating neurons rather than proliferating cells. Furthermore, total brain volume, cortical thickness and ventricle size were decreased in the irradiated embryos. At 40 weeks of age, MRI showed that the ventricles were enlarged whereas N-acetyl aspartate concentrations and functional anisotropy were reduced in the cortex of the irradiated animals, indicating a decrease in neuronal cell number and persistent neuroinflammation. Finally, in the hippocampus, we revealed a reduction in general neurogenic proliferation and in the amount of Sox2-positive precursors after radiation exposure, although only at a juvenile age.


Our findings provide evidence for a radiation-induced disruption of mouse brain development, resulting in behavioural differences. We propose that alterations in cortical morphology and juvenile hippocampal neurogenesis might both contribute to the observed aberrant behaviour. Furthermore, our results challenge the generally assumed view of a higher radiosensitivity in dividing cells. Overall, this study offers new insights into irradiation-dependent effects in the embryonic brain, of relevance for the neurodevelopmental and radiobiological field.
Description: article URL:
ISSN: 1866-1947
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biomedical MRI
Animal Physiology and Neurobiology Section - miscellaneous
Cardiovascular Imaging and Dynamics
× corresponding author
# (joint) last author

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