Department of Food and Nutrition, Hanyang University, Seoul, South Korea.
UC Davis Genome Center, University of California - Davis, Davis, California 95616, USA.
J Nutr Biochem. 2021 May;91:108599. doi: 10.1016/j.jnutbio.2021.108599. Epub 2021 Feb 3.
Early life maternal separation (MS) increases the vulnerability to depression in rats with chronic mild stress (CMS). N-3 polyunsaturated fatty acids (PUFA) improved depressive behaviors in rats with acute stress; however, their effects on rats with MS+CMS were not apparent. The purpose of the present study was to investigate the hypothesis that lifetime n-3 PUFA supplementation improves post-menopausal depression through the serotonergic and glutamatergic pathways while modulating n-3 PUFA-derived metabolites. Female rats were fed diets of either 0% n-3 PUFA during lifetime or 1% energy n-3 PUFA during pre-weaning, post-weaning, or lifetime periods. Rats were allocated to non-MS or MS groups and underwent CMS after ovariectomy. N-3 PUFA increased brain n-3 PUFA-derived endocannabinoid/oxylipin levels, and reversed depressive behaviors. N-3 PUFA decreased blood levels of adrenocorticotropic hormone and corticosterone, and brain expressions of corticotropin-releasing factor and miRNA-218, which increased the expression of the glucocorticoid receptor. N-3 PUFA decreased the expression of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and prostaglandin E, while increased the expression of miRNA-155. N-3 PUFA also increased brainstem serotonin levels and hippocampal expression of the serotonin-1A receptor, cAMP response element-binding protein (CREB), phospho-CREB, and brain-derived neurotrophic factor. However, n-3 PUFA did not affect brain expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtype 1, N-methyl-D-aspartate receptor subtype 2B, or miRNA-132. Moreover, n-3 PUFA exposure during lifetime caused greater effects than pre- and post-weaning periods. The present study suggested that n-3 PUFA improved depressive behaviors through serotonergic pathway while modulating the metabolites of n-3 PUFA in post-menopausal depressed rats with chronic stress.
早期生活中的母体分离（MS）会增加慢性轻度应激（CMS）大鼠对抑郁的易感性。n-3 多不饱和脂肪酸（PUFA）改善了急性应激大鼠的抑郁行为；然而，它们对 MS+CMS 大鼠的影响并不明显。本研究旨在验证以下假设：终生补充 n-3 PUFA 通过 5-羟色胺能和谷氨酸能途径改善绝经后抑郁症，同时调节 n-3 PUFA 衍生的代谢物。雌性大鼠终生摄入 0%n-3 PUFA 或在断奶前、断奶后或终生摄入 1%能量 n-3 PUFA 的饮食。大鼠被分配到非 MS 或 MS 组，并在卵巢切除术后进行 CMS。n-3 PUFA 增加了大脑中 n-3 PUFA 衍生的内源性大麻素/氧化应激产物的水平，并逆转了抑郁行为。n-3 PUFA 降低了血液中的促肾上腺皮质激素和皮质酮水平，以及大脑中促肾上腺皮质释放因子和 miRNA-218 的表达，这增加了糖皮质激素受体的表达。n-3 PUFA 降低了肿瘤坏死因子-α、白细胞介素（IL）-6、IL-1β 和前列腺素 E 的表达，同时增加了 miRNA-155 的表达。n-3 PUFA 还增加了脑干 5-羟色胺水平和海马 5-羟色胺 1A 受体、环磷酸腺苷反应元件结合蛋白（CREB）、磷酸化 CREB 和脑源性神经营养因子的表达。然而，n-3 PUFA 并没有影响大脑中 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚型 1、N-甲基-D-天冬氨酸受体亚型 2B 或 miRNA-132 的表达。此外，终生暴露于 n-3 PUFA 比断奶前和断奶后时期产生更大的效果。本研究表明，n-3 PUFA 通过 5-羟色胺能途径改善抑郁行为，同时调节慢性应激绝经后抑郁大鼠中 n-3 PUFA 的代谢物。
