Bennouna Djawed, Solano Melissa, Orchard Tonya S, DeVries A Courtney, Lustberg Maryam, Kopec Rachel E
Department of Human Sciences, Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA.
Neuroscience, College of Medicine, Columbus, OH 43210, USA.
Metabolites. 2019 Sep 29;9(10):208. doi: 10.3390/metabo9100208.
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, = 120) or sacrificed 10 days after the last injection (study 2, = 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 ( > 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).
化疗引起的认知障碍影响约30%的乳腺癌幸存者，但化疗如何影响脑脂质以及补充ω-3多不饱和脂肪酸如何提供保护尚不清楚。将去卵巢小鼠在食用补充2%或0% EPA+DHA的饮食后随机分为两组，分别注射两轮阿霉素+环磷酰胺或赋形剂，并在最后一次注射后4天、7天和14天处死（研究1，n = 120）或在最后一次注射后10天处死（研究2，n = 40）。研究1的全脑样本通过超高效液相色谱-串联质谱法提取和分析，以定量特异性促消退介质（SPM）。对研究2的海马提取物进行脂质组学分析，以确定脑脂质组的变化。研究1结果：所有样本中仅存在消退素D1，但未观察到浓度差异（P>0.05）。研究2结果：化疗与ω-9脂肪酸呈正相关，补充EPA+DHA有助于维持缩醛磷脂水平。未观察到化疗*饮食的统计学显著效应。结果表明SPM在化疗后脑中的作用有限，但海马脂质发生了显著改变，这些改变先前与其他认知障碍模型（即阿尔茨海默病和帕金森病）相关。
