Prenatal radiation exposure leads to higher-order telencephalic dysfunctions in adult mice that coincide with reduced synaptic plasticity and cerebral hypersynchrony

Livine Craeghs, Zsuzsanna Callaerts-Vegh, Mieke Verslegers, Ann Van der Jeugd, Kristof Govaerts, Tom Dresselaers, Elise Wogensen, Tine Verreet, Lieve Moons, Rafi Benotmane, Uwe Himmelreich, Rudi D'Hooge

Research outputpeer-review


Higher-order telencephalic circuitry has been suggested to be especially vulnerable to irradiation or other developmentally toxic impact. This report details the adult effects of prenatal irradiation at a sensitive time point on clinically relevant brain functions controlled by telencephalic regions, hippocampus (HPC), and prefrontal cortex (PFC). Pregnant C57Bl6/J mice were whole-body irradiated at embryonic day 11 (start of neurogenesis) with X-ray intensities of 0.0, 0.5, or 1.0 Gy. Female offspring completed a broad test battery of HPC-/PFC-controlled tasks that included cognitive performance, fear extinction, exploratory, and depression-like behaviors. We examined neural functions that are mechanistically related to these behavioral and cognitive changes, such as hippocampal field potentials and long-term potentiation, functional brain connectivity (by resting-state functional magnetic resonance imaging), and expression of HPC vesicular neurotransmitter transporters (by immunohistochemical quantification). Prenatally exposed mice displayed several higher-order dysfunctions, such as decreased nychthemeral activity, working memory defects, delayed extinction of threat-evoked response suppression as well as indications of perseverative behavior. Electrophysiological examination indicated impaired hippocampal synaptic plasticity. Prenatal irradiation also induced cerebral hypersynchrony and increased the number of glutamatergic HPC terminals. These changes in brain connectivity and plasticity could mechanistically underlie the irradiation-induced defects in higher telencephalic functions.
Original languageEnglish
Article numberbhab431
Pages (from-to)3525-3541
Number of pages17
JournalCerebral Cortex
Issue number16
StatePublished - 15 Aug 2022

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