The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice
5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to caus...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.762116/full |
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| author | Thomas Groves Thomas Groves Thomas Groves Christa Corley Christa Corley Stephanie D. Byrum Stephanie D. Byrum Antiño R. Allen Antiño R. Allen Antiño R. Allen |
| author_facet | Thomas Groves Thomas Groves Thomas Groves Christa Corley Christa Corley Stephanie D. Byrum Stephanie D. Byrum Antiño R. Allen Antiño R. Allen Antiño R. Allen |
| author_sort | Thomas Groves |
| collection | DOAJ |
| description | 5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to cause cognitive impairment, the synergistic effect of 5-Fu with LV has not been fully explored. The present investigation was designed to assess how the combination of 5-Fu and LV affect cognition in a murine model. Six-month-old male mice were used in this study; 15 mice received saline injections and 15 mice received 5-Fu/LV injections. One month after treatment, the elevated plus maze, Y-maze, and Morris water maze behavioral tasks were performed. Brains were then extracted, cryosectioned, and stained for CD68 to assay microglial activation and with tomato lectin to assay the vasculature. All animals were able to locate the visible and hidden platform locations in the water maze. However, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received 5-Fu/LV, but these animals showed spatial memory retention by day 5. There were no significant increases in inflammation as measured by CD68, but 5-Fu/LV treatment did modulate blood vessel morphology. Tandem mass tag proteomics analysis identified 6,049 proteins, 7 of which were differentially expressed with a p-value of <0.05 and a fold change of >1.5. The present data demonstrate that 5-Fu/LV increases anxiety and significantly impairs spatial memory retention. |
| first_indexed | 2024-12-18T02:03:51Z |
| format | Article |
| id | doaj.art-7277bd773a064c459b3b293e2b8ba165 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-18T02:03:51Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-7277bd773a064c459b3b293e2b8ba1652022-12-21T21:24:40ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-10-01810.3389/fmolb.2021.762116762116The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male MiceThomas Groves0Thomas Groves1Thomas Groves2Christa Corley3Christa Corley4Stephanie D. Byrum5Stephanie D. Byrum6Antiño R. Allen7Antiño R. Allen8Antiño R. Allen9Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesNeurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesArkansas Children’s Research Institute, Little Rock, AR, United StatesDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesNeurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to cause cognitive impairment, the synergistic effect of 5-Fu with LV has not been fully explored. The present investigation was designed to assess how the combination of 5-Fu and LV affect cognition in a murine model. Six-month-old male mice were used in this study; 15 mice received saline injections and 15 mice received 5-Fu/LV injections. One month after treatment, the elevated plus maze, Y-maze, and Morris water maze behavioral tasks were performed. Brains were then extracted, cryosectioned, and stained for CD68 to assay microglial activation and with tomato lectin to assay the vasculature. All animals were able to locate the visible and hidden platform locations in the water maze. However, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received 5-Fu/LV, but these animals showed spatial memory retention by day 5. There were no significant increases in inflammation as measured by CD68, but 5-Fu/LV treatment did modulate blood vessel morphology. Tandem mass tag proteomics analysis identified 6,049 proteins, 7 of which were differentially expressed with a p-value of <0.05 and a fold change of >1.5. The present data demonstrate that 5-Fu/LV increases anxiety and significantly impairs spatial memory retention.https://www.frontiersin.org/articles/10.3389/fmolb.2021.762116/full5-fluorouracilhippocampusneurovascularcognitionmice |
| spellingShingle | Thomas Groves Thomas Groves Thomas Groves Christa Corley Christa Corley Stephanie D. Byrum Stephanie D. Byrum Antiño R. Allen Antiño R. Allen Antiño R. Allen The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice Frontiers in Molecular Biosciences 5-fluorouracil hippocampus neurovascular cognition mice |
| title | The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice |
| title_full | The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice |
| title_fullStr | The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice |
| title_full_unstemmed | The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice |
| title_short | The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice |
| title_sort | effects of 5 fluorouracil leucovorin chemotherapy on cognitive function in male mice |
| topic | 5-fluorouracil hippocampus neurovascular cognition mice |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.762116/full |
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