Abstract
Abstract More than 18 million cancer survivors were estimated to live in the United States as of January 2022. While advances in cancer detection and treatment have substantially improved survivorship, as many as 65% of patients treated for non-central nervous system tumors may develop cancer therapy-related cognitive impairment (CRCI), a neurological disorder which includes deficits in memory, attention, multitasking, fine motor function, and information processing. Our previous work found that methotrexate (MTX) chemotherapy induces persistent neuroinflammation driving CRCI in a pediatric mouse model. We now demonstrate that the time of MTX administration, called MTX chronotherapy, induces differential microglial activation and oligodendroglial dysregulation. Furthermore, we show that MTX chronotherapy alters the amount of chemotherapy that crosses the blood-brain barrier (BBB). Current experiments are elucidating the effect of various chemotherapeutics and chronotherapy on microglial activation and crosstalk with other glia. This work will reveal crucial factors regulating CRCI-associated neuroinflammation and will define novel strategies to alleviate CRCI to prioritize quality of life for cancer survivors.
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