Kuil L E, Seigers R, Loos M, de Gooijer M C, Compter A, Boogerd W, van Tellingen O, Smit A B, Schagen S B
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Heliyon. 2024 Apr 23;10(9):e29947. doi: 10.1016/j.heliyon.2024.e29947. eCollection 2024 May 15.
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.
全脑放疗（WBRT）用于改善原发性脑肿瘤患者或各种原发性肿瘤脑转移患者的肿瘤控制情况。然而，WBRT会导致患者认知功能下降。我们使用巴恩斯迷宫评估了分次全脑放疗（fWBRT）是否会影响自动饲养笼中小鼠的自发行为和认知（空间记忆）。雄性C57Bl/6j小鼠连续5天接受双侧fWBRT，剂量为4 Gy/天。与之前的报道一致，fWBRT后4周，齿状回中双皮质素阳性细胞的免疫组织化学分析显示未成熟神经元显著减少。令人惊讶的是，自动饲养笼中测量的自发行为未受影响。此外，fWBRT后4 - 6周，用巴恩斯迷宫测量的学习和记忆也未受影响。在fWBRT后10 - 11周，观察到学习阶段逃避潜伏期存在显著差异，但在巴恩斯迷宫的探测测试中未观察到差异。总之，虽然我们证实了fWBRT后4周对神经发生有严重不良影响，但我们未发现对自动饲养笼中的自发行为或巴恩斯迷宫测量的学习能力有类似的显著影响。fWBRT的神经生物学效应与认知之间的关系似乎比通常认为的更为复杂，动物模型、认知任务、神经生物学参数和实验设置的选择可能是这类实验中的重要因素。
