Exploring the effects of maternal immune activation on cisplatin-induced toxicities.

With cancer survivorship on the rise, there needs to be more research on the long-lasting side effects that can arise from cancer treatment. Cancer treatment is associated with many side effects including fatigue, depression, and anxiety, and for some these side effects can last for years after treatment cessation. Currently, there is a lack of data predicting which patients will display severe symptoms; however, some have suggested that early-life stressors, like maternal immune activation (MIA) may contribute to these differences in susceptibility. As MIA has been associated with alterations in stress responsivity, inflammation, and metabolism, we wanted to determine if MIA would exacerbate cisplatin-induced fatigue and affective problems in adulthood. On gestational. Day 12.5, dams were injected with 20 mg/kg Poly(I:C) or vehicle. At six weeks old, offspring were single housed with running wheels and 14 days later were injected with saline or cisplatin (2.3 mg//kg/day for 5 days). After cisplatin treatment, mice underwent a battery of affective tests. MIA females showed increased voluntary wheel running compared to controls, while males did not. Following cisplatin treatment, MIA females did not show the expected decrease in running that the controls and males did. Both male and female mice showed no differences in affective tests. Our data indicate that MIA females may have been buffered from severe acute fatigue in response to cisplatin, while the males showed no effects. The increased basal activity and lack of fatigue displayed by females, may be indicative of metabolic alterations by MIA; more research needs to be done to explore this effect. MIA did not increase the susceptibility of fatigue or affective dysregulation in mice following cisplatin treatment.