Fatigue and cognitive deficits are often co-occurring symptoms reported by patients after radiation therapy for prostate cancer. In this study, we induced fatigue-like behavior in mice using targeted pelvic irradiation to mimic the clinical treatment regimen and assess cognitive behavioral changes. We observed that pelvic irradiation produced a robust fatigue phenotype, a reduced rate of spontaneous alternation in a Y-maze test, and no behavioral change in an open field test. We found that reversal learning for fatigued mice was slower with respect to time, but not with respect to effort put into the test, suggesting that fatigue may impact the ability or motivation to work at a cognitive task without impairing cognitive capabilities. In addition, we found that mice undergoing pelvic irradiation show lower whole-brain levels of mature BDNF, and that whole-brain proBDNF levels also correlate with spontaneous alternation in a Y-maze test. These results suggest that changes in BDNF levels could be both a cause and an effect of fatigue-related changes in behavior.

前列腺癌放疗后，患者通常会报告疲劳和认知缺陷。在这项研究中，我们使用有针对性的骨盆照射来诱导小鼠的疲劳样行为，以模仿临床治疗方案并评估认知行为变化。我们观察到骨盆照射产生了强大的疲劳表型，在Y迷宫测试中自发交替的频率降低，在开放视野测试中没有行为改变。我们发现，疲劳小鼠的逆向学习相对于时间而言较慢，但相对于测试所付出的努力而言却并非如此，这表明疲劳可能会影响从事认知任务的能力或动机，而不会损害认知能力。此外，我们发现进行骨盆照射的小鼠显示出较低的全脑成熟BDNF水平，在Y型迷宫测试中，全脑proBDNF的水平也与自发性交替相关。这些结果表明，BDNF水平的变化既可能是与疲劳有关的行为变化的原因，也可能是其结果。