The chemotherapeutic agent doxorubicin induces brain senescence, with modulation by APOE genotype.

ABSTRACT: Many cancer patients experience serious cognitive problems related to their treatment, which can greatly affect their quality of life. The molecular mechanisms of this cancer chemotherapy-induced cognitive impairment (CICI) are unknown, thus slowing the development of preventative approaches. We hypothesized that cancer chemotherapies could induce cellular senescence in the brain, creating a pro-inflammatory environment and damaging normal brain communication. We tested this hypothesis using the common chemotherapeutic agent doxorubicin in two independent mouse models. In the first model, we used mice that express tdTomato under the pdkn2a (p16) promoter; p16 is a regulator of cellular senescence, and its upregulation is denoted by the presence of fluorescently tagged cells. Two weeks afte

SUBMITTER: Demby T 

PROVIDER: S-EPMC11302516 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature