Page Kathleen C, Anday Endla K
Department of Biology, Bucknell University, Lewisburg, PA, United States.
College of Medicine, Drexel University, Philadelphia, PA, United States.
Front Neurosci. 2020 Sep 11;14:527258. doi: 10.3389/fnins.2020.527258. eCollection 2020.
Maternal and postnatal diets result in long-term changes in offspring brain and behavior; however, the key mediators of these developmental changes are not well-defined. In this study, we investigated the impact of maternal and post-weaning high-fat diets on gene expression of key components mediating hippocampal synaptic efficacy. In addition, we evaluated the risk for impaired stress-coping and anxiety-like behaviors in adult offspring exposed to obesogenic diets during early life.
Dams were fed a control (C) or high-fat (HF) diet prior to mating, pregnancy, and lactation. Male offspring from control chow and high-fat fed dams were weaned to control chow or HF diets. The forced swim test (FST) and the elevated-plus maze (EPM) were used to detect stress-coping and anxiety-like behavior, respectively. Real-time RT-PCR and ELISA were used to analyze hippocampal expression of genes mediating synaptic function.
Animals fed a HF diet post-weaning spent more time immobile in the FST. Swimming time was reduced in response to both maternal and post-weaning HF diets. Both maternal and post-weaning HF diets contributed to anxiety-like behavior in animals exposed to the EPM. Maternal and post-weaning HF diets were associated with a significant decrease in mRNA and protein expression for hippocampal GDNF, MAP2, SNAP25, and synaptophysin. Hippocampal mRNA expression of key serotonergic and glutamatergic receptors also exhibited differential responses to maternal and post-weaning HF diets. Hippocampal serotonergic receptor 5HT1A mRNA was reduced in response to both the maternal and post-weaning diet, whereas, 5HT2A receptor mRNA expression was increased in response to the maternal HF diet. The glutamate AMPA receptor subunit, GluA1, mRNA expression was significantly reduced in response to both diets, whereas no change was detected in GluA2 subunit mRNA expression.
These data demonstrate that the expression of genes mediating synaptic function are differentially affected by maternal and post-weaning high-fat diets. The post-weaning high-fat diet clearly disturbs both behavior and gene expression. In addition, although the transition to control diet at weaning partially compensates for the adverse effects of the maternal HF diet, the negative consequence of the maternal HF diet is exacerbated by continuing the high-fat diet post-weaning. We present evidence to support the claim that these dietary influences increase the risk for anxiety and impaired stress-coping abilities in adulthood.
母体饮食和产后饮食会导致后代大脑和行为的长期变化；然而，这些发育变化的关键介导因素尚未明确。在本研究中，我们调查了母体高脂饮食和断奶后高脂饮食对介导海马突触效能的关键成分基因表达的影响。此外，我们评估了早年暴露于致肥胖饮食的成年后代出现应激应对受损和焦虑样行为的风险。
在交配、怀孕和哺乳前，给母鼠喂食对照（C）饮食或高脂（HF）饮食。将来自对照饲料喂养和高脂饲料喂养母鼠的雄性后代断奶后分别喂食对照饲料或高脂饮食。强迫游泳试验（FST）和高架十字迷宫试验（EPM）分别用于检测应激应对和焦虑样行为。实时逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）用于分析介导突触功能的基因在海马中的表达。
断奶后喂食高脂饮食的动物在FST中静止不动的时间更长。母体和断奶后高脂饮食均导致游泳时间减少。母体和断奶后高脂饮食均导致暴露于EPM的动物出现焦虑样行为。母体和断奶后高脂饮食与海马胶质细胞源性神经营养因子（GDNF）、微管相关蛋白2（MAP2）、突触小体相关蛋白25（SNAP25）和突触素的mRNA和蛋白表达显著降低有关。关键的5-羟色胺能和谷氨酸能受体的海马mRNA表达对母体和断奶后高脂饮食也表现出不同的反应。母体和断奶后饮食均导致海马5-羟色胺能受体5HT1A mRNA表达降低，而母体高脂饮食导致5HT2A受体mRNA表达增加。谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluA1的mRNA表达在两种饮食作用下均显著降低，而GluA2亚基mRNA表达未检测到变化。
这些数据表明，介导突触功能的基因表达受到母体和断奶后高脂饮食的不同影响。断奶后高脂饮食明显扰乱了行为和基因表达。此外，尽管断奶时转为对照饮食可部分补偿母体高脂饮食的不利影响，但断奶后继续高脂饮食会加剧母体高脂饮食的负面后果。我们提供的证据支持以下观点：这些饮食影响会增加成年期焦虑和应激应对能力受损的风险。
