Fractionated brain X-irradiation profoundly reduces hippocampal immature neuron numbers without affecting spontaneous behavior in mice

L. E. Kuil, R. Seigers, M. Loos, M. C. de Gooijer, A. Compter, W. Boogerd, O. van Tellingen, A. B. Smit, S. B. Schagen*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Whole brain radiotherapy (WBRT) is used to improve tumor control in patients with primary brain tumors, or brain metastasis from various primary tumors to improve tumor control. However, WBRT can lead to cognitive decline in patients. We assessed whether fractionated WBRT (fWBRT) affects spontaneous behavior of mice in automated home cages and cognition (spatial memory) using the Barnes maze. Male C57Bl/6j mice received bi-lateral fWBRT at a dosage of 4 Gy/day on 5 consecutive days. In line with previous reports, immunohistochemical analysis of doublecortin positive cells in the dentate gyrus showed a profound reduction in immature neurons 4 weeks after fWBRT. Surprisingly, spontaneous behavior as measured in automated home cages was not affected. Moreover, learning and memory measured with Barnes maze, was also not affected 4–6 weeks after fWBRT. At 10–11 weeks after fWBRT a significant difference in escape latency during the learning phase, but not in the probe test of the Barnes maze was observed. In conclusion, although we confirmed the serious adverse effect of fWBRT on neurogenesis 4 weeks after fWBRT, we did not find similar profound effects on spontaneous behavior in the automated home cage nor on learning abilities as measured by the Barnes maze. The relationship between the neurobiological effects of fWBRT and cognition seems more complex than often assumed and the choice of animal model, cognitive tasks, neurobiological parameters, and experimental set-up might be important factors in these types of experiments.

Original languageEnglish
Article numbere29947
Pages (from-to)1-10
Number of pages10
JournalHeliyon
Volume10
Issue number9
Early online date23 Apr 2024
DOIs
Publication statusPublished - 15 May 2024

Bibliographical note

Publisher Copyright:
© 2024

Funding

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sanne Schagen reports financial support for the study was provided by KWF. However, the KWF did not influence the design, execution or data analysis performed in this study. All other authors declare that they have no conflict of interest.

FundersFunder number
KWF Kankerbestrijding

    Keywords

    • Cancer
    • Cognition
    • Learning
    • Radiotherapy
    • Therapy-induced cognitive impairment

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