A role for orexin in cytotoxic chemotherapy-induced fatigue.

摘要: Fatigue is the most common symptom related to cytotoxic chemotherapeutic treatment of cancer. Peripheral inflammation associated with chemotherapy likely a causal factor fatigue. The neural mechanisms by which induces fatigue behavior are not known. This lack knowledge hinders development interventions reduce or prevent this disabling symptom. Infection induced fatigue/lethargy in rodents mediated suppression hypothalamic orexin activity. Orexin critical for maintaining wakefulness and motivated behavior. Though there differences between infection some symptoms, both induce peripheral Based on these similarities we hypothesized that disrupting neuron We found single dose cocktail (cyclophosphamide, adriamycin, 5-fluorouracil - CAF) mice rats as evidenced significant decline voluntary locomotor activity measured telemetry. CAF inflammatory gene expression IL-1R1 (p<0.001), IL-6 (p<0.01), TNFα MCP-1 (p<0.05) rodent hypothalamus 6-24h after during maximum fatigue/lethargy. decreased reflected nuclear cFos localization neurons 24h orexin-A cerebrospinal fluid 16 h (p<0.001). Most importantly, central administration 1 μg restored CAF-treated (p<0.05). These results demonstrate has role chemotherapy-induced rodents.