Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Authors

Tonya S. Orchard, The Ohio State UniversityFollow
Monica M. Gaudier-Diaz, University of North Carolina at Chapel HillFollow
Panchita Phuwamongkolwiwat-Chu, The Ohio State UniversityFollow
Rebecca Andridge, The Ohio State UniversityFollow
Maryam B. Lustberg, The Ohio State UniversityFollow
Joshua Bomser, The Ohio State UniversityFollow
Rachel M. Cole, The Ohio State UniversityFollow
Martha A. Belury, The Ohio State UniversityFollow
Courtney A. DeVries, West Virginia UniversityFollow

Author ORCID Identifier

https://orcid.org/0000-0002-7265-7314

https://orcid.org/0000-0002-1531-864X

https://orcid.org/0000-0002-9000-8721

https://orcid.org/0000-0001-9991-9647

https://orcid.org/0000-0001-8559-5645

https://orcid.org/0000-0002-8523-1646

N/A

https://orcid.org/0000-0002-6480-4281

https://orcid.org/0000-0002-2721-096X

Document Type

Article

Publication Date

2018

College/Unit

School of Medicine

Department/Program/Center

Neurology

Abstract

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions.

Digital Commons Citation

Orchard, Tonya S.; Gaudier-Diaz, Monica M.; Phuwamongkolwiwat-Chu, Panchita; Andridge, Rebecca; Lustberg, Maryam B.; Bomser, Joshua; Cole, Rachel M.; Belury, Martha A.; and DeVries, Courtney A., "Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy" (2018). Faculty & Staff Scholarship. 1288.
https://researchrepository.wvu.edu/faculty_publications/1288

Source Citation

Orchard, T., Gaudier-Diaz, M., Phuwamongkolwiwat-Chu, P., Andridge, R., Lustberg, M., Bomser, J., Cole, R., Belury, M., & DeVries, A. (2018). Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy. Nutrients, 10(12), 2004. https://doi.org/10.3390/nu10122004

Comments

1. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).