Abstract # 3114 Neuroinflammation and chemotherapy-related fatigue

Abstract

Fatigue is a highly prevalent and undertreated comorbidity associated with chemotherapy treatment. Neuroinflammation is hypothesized to be one of the leading mechanisms underlying chemotherapy-related fatigue. Indeed, neuroinflammation is associated with the development of an array of behavioral deficits including fatigue. This experiment tested the hypothesis that chemotherapy-related fatigue is associated with microglia activation and cytokine production. Female 8–9 week old Balb/c mice had emitters surgically implanted into the peritoneal cavity to measure passive movement and access to a running wheel to measure motivated movement. Half of the mice received a total of six injections of 30 mg/kg (n = 8) paclitaxel chemotherapy or vehicle (n = 8), which were administered every other day over two weeks. Additional mice, receiving identical chemotherapy treatments without access to wheels and emitters were used to collect tissue at additional time points post-treatment. Chemotherapy transiently reduced locomotion and wheel running during treatment but resulted in hyperactivity in the 1–3 weeks post-treatment. Microglia and astrocyte reactivity will be measured in the hippocampus, hypothalamus, and prefrontal cortex using IBA-1 and GFAP immunohistochemistry, respectively. mRNA of inflammatory cytokines (TNF α , IL-1 β , and IL-6) will be measured in these same brain regions using qRT-PCR and their circulating protein expression will be quantified in plasma samples using multiplex ELISA technology. Microglia activation will be analyzed for correlation with changes in passive and motivated locomotion.