451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation
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 cognit...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2023-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866123004776/type/journal_article |
| _version_ | 1827960790636822528 |
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| author | Amber M. Asher David A. Morilak |
| author_facet | Amber M. Asher David A. Morilak |
| author_sort | Amber M. Asher |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T16:15:12Z |
| format | Article |
| id | doaj.art-e8751001241a4715b608e891d03959cf |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-09T16:15:12Z |
| publishDate | 2023-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-e8751001241a4715b608e891d03959cf2023-04-24T05:55:57ZengCambridge University PressJournal of Clinical and Translational Science2059-86612023-04-01713413410.1017/cts.2023.477451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammationAmber M. Asher0David A. Morilak1University of Texas Health San AntonioUniversity of Texas Health San AntonioOBJECTIVES/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.https://www.cambridge.org/core/product/identifier/S2059866123004776/type/journal_article |
| spellingShingle | Amber M. Asher David A. Morilak 451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation Journal of Clinical and Translational Science |
| title | 451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation |
| title_full | 451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation |
| title_fullStr | 451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation |
| title_full_unstemmed | 451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation |
| title_short | 451 Interactions between tumor, age, and chemotherapy in cognitive impairments and neuroinflammation |
| title_sort | 451 interactions between tumor age and chemotherapy in cognitive impairments and neuroinflammation |
| url | https://www.cambridge.org/core/product/identifier/S2059866123004776/type/journal_article |
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