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451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation

Published online by Cambridge University Press:  24 April 2023

Amber M. Asher
Affiliation:
University of Texas Health San Antonio
David A. Morilak
Affiliation:
University of Texas Health San Antonio
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Abstract

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OBJECTIVES/GOALS: We will use a novel syngeneic model of prostate cancer to examine impairments and uncover potential changes in inflammatory signaling in the brains of animals with and without tumors. We will then investigate the interaction between peripheral tumor, age, and chemotherapy on cognitive impairments and any accompanying neuroinflammation METHODS/STUDY POPULATION: Male Copenhagen rats (aged 3 or 10 months) were subjected to tumor fragment implantation (Dunning R2237G cells) or sham surgery. Once tumors were palpable, animals received either docetaxel (4.5mg/kg, intraperitoneal) or it’s vehicle once every other day for 5 days (3 injections total) followed by a two-week recovery period. During this time, TNFa and IL-6 was quantified in plasma samples obtained once per week for two weeks. Hippocampal-mediated visuospatial and working memories were assessed using the novel object task and percent alternation in a y-maze, respectively. Afterwards, trunk blood and hippocampal tissue were isolated. TNFa and IL-6 protein was quantified in plasma. Hippocampal tissue was probed for markers of neuroinflammation, including increases in TNFa, IL-6, and reactive microglia RESULTS/ANTICIPATED RESULTS: The presence of a tumor alone produces deficits in hippocampal-mediated visuospatial memory and working memory regardless of treatment and persistent elevations in TNFa and IL-6 in plasma. Docetaxel administration also produces impairments in hippocampal-mediated visuospatial memory, but not in working memory. We anticipate these cognitive impairments will be accompanied by hippocampal neuroinflammation. We expect age and docetaxel chemotherapy to exacerbate working memory deficits and markers in hippocampal neuroinflammation, including increases in TNFa, IL-6 and reactive microglia DISCUSSION/SIGNIFICANCE: This study will provide insight into the interaction between tumor, age, and chemotherapy in impairments in visuospatial memories. This model provides a substrate upon which interventions can be tested to ensure the efficacy of the cancer treatment is maintained when treating these cognitive impairments.

Type
Team Science
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2023. The Association for Clinical and Translational Science