The implications of poor maternal diet on offspring metabolic and neuroimmune development are well established. Increasing evidence now suggests that maternal obesity and poor diet can also increase the risk of postpartum mood disorders, but the mechanisms are unknown. Here we investigated the effects of a poor, high-fat-high-sugar diet (HFSD) on peripheral and central inflammation, neurogenesis and postpartum anxiety-like behaviours. We hypothesised that long-term consumption of a HFSD pre- and post-conception would increase the levels of circulating cytokines and induce microglial activation, particularly in the arcuate nucleus of the hypothalamus (ARC), as the primary brain region involved in the integration of satiety signalling; and this would lead to increased anxiety, stress responsivity and disrupted neurogenesis. We further hypothesised that these effects would be ameliorated by consumption of a healthier diet during pregnancy – specifically a diet high in omega-3 polyunsaturated fatty acids (PUFAs). As expected, the HFSD significantly increased pre-conception body weight, elevated circulating cytokines and activated microglia in the ARC, as well as in the basolateral amygdala. The HFSD also significantly increased the numbers of immature (doublecortin (DCX)-positive) neurons in the subgranular/granular region of the hippocampus, a neurogenic response that was, surprisingly, mimicked by consumption of a diet high in omega-3 PUFAs. Despite these effects of peri-pregnancy dietary imbalance, we detected no differences in anxiety-like behaviours or hypothalamic-pituitary-adrenal (HPA) axis reactivity between the groups. A shift to a healthier diet post-conception reversed the peripheral inflammation and alleviated the microglial activation. These novel data indicate the importance of a balanced peri-pregnancy diet and highlight the need for future research into key triggers that alter the neuroimmune balance in the maternal brain.

母亲饮食不良对后代代谢和神经免疫发育的影响已得到充分证实。现在越来越多的证据表明，母亲肥胖和不良饮食也会增加产后情绪障碍的风险，但其机制尚不清楚。在这里，我们研究了不良的高脂肪高糖饮食 (HFSD) 对外周和中枢炎症、神经发生和产后焦虑样行为的影响。我们假设在受孕前和受孕后长期食用 HFSD 会增加循环细胞因子的水平并诱导小胶质细胞激活，特别是在下丘脑弓状核 (ARC) 中，作为参与整合的主要大脑区域饱腹感信号；这会导致焦虑、压力反应性增加和神经发生中断。我们进一步假设，在怀孕期间食用更健康的饮食会改善这些影响 - 特别是富含 omega-3 多不饱和脂肪酸 (PUFA) 的饮食。正如预期的那样，HFSD 显着增加了受孕前的体重，增加了 ARC 以及基底外侧杏仁核中的循环细胞因子和活化的小胶质细胞。HFSD 还显着增加了海马颗粒下/颗粒区域未成熟（双皮质素 (DCX) 阳性）神经元的数量，这是一种神经源性反应，令人惊讶的是，通过食用富含 omega-3 多不饱和脂肪酸的饮食来模拟。尽管围孕期饮食不平衡有这些影响，但我们没有发现两组之间的焦虑样行为或下丘脑-垂体-肾上腺 (HPA) 轴反应性存在差异。受孕后转向更健康的饮食可以逆转外周炎症并减轻小胶质细胞的激活。这些新数据表明了平衡的围孕期饮食的重要性，并强调了未来对改变母体大脑神经免疫平衡的关键触发因素进行研究的必要性。