Effects of Paclitaxel Chemotherapy on Central and Peripheral Inflammation
Poster
Abstract
Cognitive impairment in cancer patients is often aggravated by treatments such as chemotherapy. The reduced quality of life attributed to these impairments often results in the discontinuation of treatment among patients and poorer long-term prognosis. Elevated circulating concentrations of stress hormone, corticosterone (CORT), and inflammatory markers are associated with enhanced fatigue and poorer cognitive capabilities in cancer patients. However, the neural cause of these debilitating symptoms remains unknown.
In this study, chemotherapy was hypothesized to increase corticosterone and increase inflammation in the brain itself in C57Bl/6 mice. Six doses of paclitaxel chemotherapy were administered to a test group of mice while a parallel group received control (vehicle) injections. Brains and spleens were collected following chemotherapy to examine central and peripheral inflammatory markers. Blood was analyzed for changes in circulating CORT and cytokine concentrations. Finally, mice were tested for cognitive function using contextual fear conditioning, a hippocampal-dependent memory task in which mice were required to remember an aversive environment as assessed by stereotypical fear behavior (i.e., “freezing”).
Chemotherapy-treated mice froze less than vehicle-treated mice, indicating impaired memory. CORT levels were elevated in chemo-treated mice compared to vehicle mice. Immunohistochemistry of central immune cell markers (Iba1 for microglia, GFAP for astrocytes) will be analyzed in brain slices containing the hippocampus to identify the extent to which chemotherapy induces neuroinflammation in this region. RNA will also be analyzed from the spleen to identify the extent to which a source of peripheral inflammation is increased by chemotherapy. By understanding potential underlying mechanisms of behavioral comorbidities in cancer patients, this work may lead to better treatment prognoses in this population.
Great job on your first poster from the lab, Kylie! So nice to see these data put together and explained in such a concise, clear manner.