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

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Abstract

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.

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Acknowledgements

We would like to thank the (Institute of Neuroscience, Soochow University) for technical support.

Funding

This work was supported by the Science Foundation of Jiangsu Commission of Health (H2018116), Jiangsu Planned Projects for Postdoctoral Research Funds (2018K259C).

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Authors and Affiliations

  1. Department of Radiotherapy and Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

    Xin Ding, Hai-Bo Zhang, Hui Qiu, Xin Wen & Long-zhen Zhang

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  1. Xin Ding
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Correspondence to Xin Ding.

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Ding, X., Zhang, HB., Qiu, H. et al. Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus. Childs Nerv Syst 38, 1867–1875 (2022). https://doi.org/10.1007/s00381-022-05646-w

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