Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus

Objective Therapeutic irradiation is commonly used to treat brain cancers but can induce cognitive dysfunction, especially in children. The mechanism is unknown but likely involves alterations in dendritic spine number and structure. Methods To explore the impact of radiation exposure on the alteration of dendritic spine morphology in the hippocampus of young brains, 21-day-old Sprague-Dawley rats received cranial irradiation (10 Gy), and changes in spine density and morphology in dentate gyrus (DG) granules and CA1 pyramidal neurons were detected 1 and 3 months later by using Golgi staining. Moreover, we analyzed synapse-associated proteins within dendritic spines after irradiation. Result Our data showed that cognitive deficits were detected in young rats at both time points postirradiation, accompanied by morphological changes in dendritic spines. Our results revealed significant reductions in spine density in the DG at both 1 month (40.58%) and 3 months (28.92%) postirradiation. However, there was a decrease in spine density only at 1 month (33.29%) postirradiation in the basal dendrites of CA1 neurons and no significant changes in the apical dendrites of CA1 neurons at either time point. Notably, among our findings were the significant dynamic changes in spine morphology that persisted 3 months following cranial irradiation. Meanwhile, we found that depletion of the synapse-associated proteins PSD95 and Drebrin coincided with alterations in dendritic spines. Conclusion These data suggest that the decreased levels of PSD95 and Drebrin after ionizing radiation may cause changes in synaptic plasticity by affecting the morphological structure of dendritic spines, blocking the functional connectivity pathways of the brain and leading to cognitive impairment. Although the mechanism involved is unclear, understanding how ionizing radiation affects young brain hippocampal tissue may be useful to gain new mechanistic insights into radiation-induced cognitive dysfunction.

Automated summary

Young rats showed cognitive deficits and morphological changes in dendritic spines at both 1 and 3 months postirradiation. Significant reductions in spine density were observed in the DG at both time points, as well as a decrease in spine density in the basal dendrites of CA1 neurons only at 1 month postirradiation. Dynamic changes in spine morphology were found to persist 3 months following cranial irradiation.