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Physiological and Cognitive Changes after Treatments of Cyclophosphamide, Methotrexate, and Fluorouracil: Implications of the Gut Microbiome and Depressive-Like Behavior

ABSTRACT: 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 considered to be a potential mechanism behind chemobrain. Here we investigate the association between anxiety and despair-like behaviors in mice treated with cyclophosphamide, methotrexate, and fluorouracil along with host histological, proteomic, gene expression, and gut microbial responses. Forced swim and sociability tests were used to evaluate depression and despair like behaviors. Tandem mass tag proteomics approach was used to assess changes in neural protein network of the amygdala and hippocampus. While quantitative reverse transcription polymerase chain reaction, we evaluated changes in intestinal gap junction markers. Finally, the composition of gut microbiota was assessed through 16S rRNA gene sequencing. We have 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 as a result of CMF treatment. Finally, we observed immediate changes in the microbial population after chemotherapy treatment, with a notable increase in the mucinophilic bacteria Akkermansia mucinophila.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Antino Allen

PROVIDER: MSV000092957 | MassIVE |

SECONDARY ACCESSION(S): PXD045672

REPOSITORIES: MassIVE

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Physiological and Cognitive Changes after Treatments of Cyclophosphamide, Methotrexate, and Fluorouracil: Implications of the Gut Microbiome and Depressive-Like Behavior

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