Selina Vickery – Neuroscience

Effects of Voluntary Exercise on Chemotherapy-Induced Anxiety and Neuroinflammation in Mice

Selina Vickery Spring Festival Poster

Abstract

Background: Chemotherapy is associated with severe and debilitating comorbidities, including anxiety, which can last years beyond the completion of treatment, reducing patient quality of life and ultimately increasing mortality. Chemotherapy activates the immune system in both patient and rodent models, including increases in neuroinflammatory signals characterized by increases in cytokine expression. Cytokines are associated with changes in anxiety-like behavior in rodents. Moderate exercise (e.g., 5 times/week, 30 min treadmill walking) has been shown to attenuate anxiety in breast cancer patients and decrease neuroinflammation in healthy rodent models. However, the anti-inflammatory mechanisms of exercise on chemotherapy-induced neuroinflammation and anxiety remain unknown. We hypothesized that voluntary exercise decreases chemotherapy-induced anxiety-like behaviors by reducing neuroinflammation in a mouse model.
Methods: Sixty healthy, 8-9 week-old adult, female C57/Bl6 mice (1/cage) were housed with a locked or unlocked running wheel. Half of each of these groups received chemotherapy (30 mg/kg paclitaxel; i.p.), the other half received vehicle (1:1 Cremophor EL:PBS) injections every other day for a total of 6 doses starting after a 1-week acclimation period to running wheels (n=15/group). Eight days after the final dose, the mice underwent behavioral testing (open field and elevated plus maze) for anxiety-like behavior. The next day they were euthanized, and their brains collected for neuroimmunological assessment. Pro-inflammatory gene expression (Il-1B, Tnfa, Icam-1, Cxcl-1) was measured via RT-qPCR in brain regions associated with anxiety-like behaviors (hippocampus, hypothalamus, prefrontal cortex).
Results and conclusions: Chemotherapy caused a reduction in body mass which was attenuated by voluntary running while food intake within treatment groups remained steady. Wheel-running decreased anxiety-like behavior in vehicle treated mice as measured by open field central tendency. Chemotherapy decreased the number of entries to open arms in the elevated plus maze within the locked cohorts only. In the future, analysis of behavior and cytokine expression at an earlier time point may be done to investigate more acute interactions of voluntary exercise on chemotherapy-related anxiety-like behavior. Identifying the mechanisms underlying chemotherapy-associated behavioral comorbidities is essential to potentially develop cost-effective, non-invasive, and non-pharmaceutical approaches to treating anxiety in cancer patients and survivors.