Abstract
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.
