The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids
Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections o...
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MDPI AG
2019-09-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/9/10/208 |
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| author | Djawed Bennouna Melissa Solano Tonya S. Orchard A. Courtney DeVries Maryam Lustberg Rachel E. Kopec |
| author_facet | Djawed Bennouna Melissa Solano Tonya S. Orchard A. Courtney DeVries Maryam Lustberg Rachel E. Kopec |
| author_sort | Djawed Bennouna |
| collection | DOAJ |
| description | Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, <i>n</i> = 120) or sacrificed 10 days after the last injection (study 2, <i>n</i> = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (<i>P</i> > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease). |
| first_indexed | 2024-12-12T23:40:38Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-12-12T23:40:38Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-c5acbf2fa815456b837c590e2f12e6b32022-12-22T00:07:11ZengMDPI AGMetabolites2218-19892019-09-0191020810.3390/metabo9100208metabo9100208The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain LipidsDjawed Bennouna0Melissa Solano1Tonya S. Orchard2A. Courtney DeVries3Maryam Lustberg4Rachel E. Kopec5Department of Human Sciences, Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USADepartment of Human Sciences, Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USADepartment of Human Sciences, Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USANeuroscience, College of Medicine, Columbus, OH 43210, USACollege of Medicine, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Human Sciences, Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USAChemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, <i>n</i> = 120) or sacrificed 10 days after the last injection (study 2, <i>n</i> = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (<i>P</i> > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease).https://www.mdpi.com/2218-1989/9/10/208specialized pro-resolving mediatorshippocampusepadhalipidomicschromatographymass spectrometry |
| spellingShingle | Djawed Bennouna Melissa Solano Tonya S. Orchard A. Courtney DeVries Maryam Lustberg Rachel E. Kopec The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids Metabolites specialized pro-resolving mediators hippocampus epa dha lipidomics chromatography mass spectrometry |
| title | The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids |
| title_full | The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids |
| title_fullStr | The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids |
| title_full_unstemmed | The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids |
| title_short | The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids |
| title_sort | effects of doxorubicin based chemotherapy and omega 3 supplementation on mouse brain lipids |
| topic | specialized pro-resolving mediators hippocampus epa dha lipidomics chromatography mass spectrometry |
| url | https://www.mdpi.com/2218-1989/9/10/208 |
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