Implications of Cyclophosphamide, Methotrexate, and 5-Flurouracil Chemotherapy on Hippocampal-Dependent Cognition and Gut-Microbiome

Cancer survivors often experience chemotherapy-induced cognitive impairment, often referred to as "chemobrain". Which can decrease the quality-of-life of most patients post-chemotherapy. Here we evaluate the potential mechanisms for long-term symptoms in cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-induced cognitive impairments and implications of CMF on the microbiome. Twelve-week-old C57/B6J female mice were treated with a combination of CMF once a week for 4 weeks. Spatial memory was tested with the Morris water maze. Hippocampal tissues were used to probe for immediate-early genes (IEGs) with western blotting techniques. Fecal matter was collected to assess microbial community composition via 16S rRNA gene sequencing. In this study, we showed that chemotherapy impaired spatial memory during the Morris water maze trials and resulted in a significant decrease in immediate early genes (IEGs) c-Fos, Arc, and Zif286 expression. Changes in microbial diversity were minor or not significant. These results suggest that continual memory deficits may be associated with alterations in synaptic plastic ity and long-term potentiation.