Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.
Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.
J Nutr Biochem. 2020 Oct;84:108417. doi: 10.1016/j.jnutbio.2020.108417. Epub 2020 May 19.
Stress and ovarian hormone fluctuation are risk factors for postpartum depression (PPD). Previous studies suggested antidepressant-like effects of n-3 polyunsaturated fatty acids (PUFA), but their effect on dam animal with additional stress were not clear. The purpose of the present study was to investigate the hypothesis that n-3 PUFA improved PPD through the serotonergic and glutamatergic pathways by modulating miRNA. Rats were fed n-3 PUFA or control diet from gestation, with pup separation (PS) on postpartum days 2-14 and non-PS controls. N-3 PUFA reversed PS-induced depressive behaviors, including increased immobility, latencies to contact first pup and retrieve all pups, and decreased sucrose preference. N-3 PUFA also modulated the hypothalamic-pituitary-adrenal (HPA) axis by decreasing circulating levels of adrenocorticotropic hormone and corticosterone and expression of hypothalamic corticotrophin releasing factor and hippocampal miRNA-218 but increasing the hippocampal expression of glucocorticoid receptor. N-3 PUFA inhibited neuroinflammation by decreasing circulating levels of prostaglandin E and hippocampal expression of tumor necrosis factor-α, interleukin-6, and miRNA-155. In addition, n-3 PUFA up-regulated the serotonergic pathway by increasing circulating levels of serotonin and hippocampal expression of serotonin-1A receptor, cAMP response element binding protein (CREB), pCREB, brain-derived neurotrophic factor, and miRNA-182 but did not affect the glutamatergic pathway according to the hippocampal expression of N-methyl-D-aspartate receptor-2B. The present study suggested that n-3 PUFA improved PPD through the serotonergic pathway by modifying the HPA axis, neuroinflammation, and related miRNAs.
应激和卵巢激素波动是产后抑郁症（PPD）的危险因素。先前的研究表明，n-3 多不饱和脂肪酸（PUFA）具有抗抑郁作用，但它们对有额外应激的母鼠的影响尚不清楚。本研究旨在通过调节 miRNA 来验证 n-3 PUFA 通过 5-羟色胺能和谷氨酸能途径改善 PPD 的假说。从妊娠开始，大鼠喂养 n-3 PUFA 或对照饮食，产后第 2-14 天进行幼仔分离（PS）和非 PS 对照。n-3 PUFA 逆转了 PS 诱导的抑郁行为，包括增加不动性、首次接触幼仔和取回所有幼仔的潜伏期，以及降低蔗糖偏好。n-3 PUFA 还通过降低循环促肾上腺皮质激素和皮质酮水平以及下丘脑促肾上腺皮质激素释放因子和海马 miRNA-218 的表达，同时增加糖皮质激素受体的表达，调节下丘脑-垂体-肾上腺（HPA）轴。n-3 PUFA 通过降低循环前列腺素 E 和海马肿瘤坏死因子-α、白细胞介素-6 和 miRNA-155 的表达来抑制神经炎症。此外，n-3 PUFA 通过增加循环 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）、pCREB、脑源性神经营养因子和 miRNA-182 的表达来上调 5-羟色胺能途径，但不影响谷氨酸能途径，这是根据海马 N-甲基-D-天冬氨酸受体-2B 的表达情况得出的。本研究表明，n-3 PUFA 通过调节 HPA 轴、神经炎症和相关 miRNA 来改善 PPD 通过 5-羟色胺能途径。
