Chemotherapy-induced physiological, cognitive, and gut microbial changes.

Chemotherapy-induced cognitive impairment, colloquially referred to as chemobrain, is a poorly understood phenomenon affecting a highly variable proportion of patients with breast cancer. Inflammation, a condition associated with many pathologies, is a potential mechanism behind chemobrain. Here we investigate the association between anxiety and despair-like behaviors in mice treated with cyclophosphamide, methotrexate, and fluorouracil (CMF) along with host histological, proteomic, gene expression, and gut microbial responses. Forced swim and sociability (insert name of test here) tests were used to evaluate depression and despair-like behaviors. Tandem mass tag (TMT) proteomics approach was used to assess changes in neural protein network of the amygdala and hippocampus. While quantitative reverse transcription polymerase chain reaction (qRT-PCR), we evaluated changes in intestinal gap junction markers. Finally, the composition of gut microbiota was assessed through 16S rRNA gene sequencing. We've observed that CMF induced social and despair-like behavior in mice 96 hours following treatment. Proteomic analysis identified changes various proteins related to progressive neurological disease, working memory deficit, primary anxiety disorder and gene expression revealed increases in NDMA and AMPA receptors in both the hippocampus and the amygdala because of CMF treatment. We observed immediate changes in the microbial population after chemotherapy treatment