In utero X-ray exposure disturbs normal brain development by reducing the number and impairing the migration of inhibitory interneurons

The brain is a complex structure mainly consisting of excitatory projection neurons and inhibitory interneurons (INs). Both cell types regulate the excitation/inhibition (E/I) balance, which is crucial for proper brain functioning. Genetic and environmental factors may disturb the E/I balance and lead to the development of neurodevelopmental disorders, such as epilepsy. Currently, the effect of environmental disturbances during early brain development on IN migration and cortical positioning remains elusive. Therefore, we investigate whether in utero X-ray exposure affects the migration and cortical positioning of INs. We hypothesize that X-ray exposure at embryonic day (E) 11 impairs the migration and final position of somatostatin (SST)-INs and parvalbumin (PV)-INs in the cerebral cortex of mice. After exposing pregnant dams to X-rays, INs were analyzed using (acute) brain slice preparations with time-lapse microscopy and immunohistochemistry. Our results show a reduced IN migration speed and number in embryonic brains after X-ray exposure. Moreover, X-ray exposure diminishes the number of SST-INs and PV-INs in 8-weekold mouse brains, contributing to a reduced cortical thickness. Besides, the cortical position of SST-INs and PV-INs was not disturbed. These results suggest that early-life X-ray exposure impairs normal brain development by disturbing the migration and number of INs.