Department of Toxicology, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, PL, Poland.
Department of Pharmacodynamics, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, PL, Poland.
Mol Neurobiol. 2022 Sep;59(9):5695-5721. doi: 10.1007/s12035-022-02908-1. Epub 2022 Jul 1.
The problem of an unbalanced diet, overly rich in fats, affects a significant proportion of the population, including women of childbearing age. Negative metabolic and endocrine outcomes for offspring associated with maternal high-fat diet during pregnancy and/or lactation are well documented in the literature. In this paper, we present our findings on the little-studied effects of this diet on NMDA receptors and cognitive functions in offspring. The subject of the study was the rat offspring born from dams fed a high-fat diet before mating and throughout pregnancy and lactation. Using a novel object location test, spatial memory impairment was detected in adolescent offspring as well as in young adult female offspring. The recognition memory of the adolescent and young adult offspring remained unaltered. We also found multiple alterations in the expression of the NMDA receptor subunits, NMDA receptor-associated scaffolding proteins, and selected microRNAs that regulate the activity of the NMDA receptor in the medial prefrontal cortex and the hippocampus of the offspring. Sex-dependent changes in glutamate levels were identified in extracellular fluid obtained from the medial prefrontal cortex and the hippocampus of the offspring. The obtained results indicate that a maternal high-fat diet during pregnancy and lactation can induce in the offspring memory disturbances accompanied by alterations in NMDA receptor expression.
饮食不平衡，脂肪含量过高的问题影响了相当一部分人群，包括育龄妇女。文献中充分记录了与母亲在怀孕期间和/或哺乳期高脂肪饮食相关的后代代谢和内分泌的负面后果。在本文中，我们介绍了我们关于这种饮食对 NMDA 受体和后代认知功能的研究结果。研究对象是在交配前、怀孕期间和哺乳期喂食高脂肪饮食的母鼠所生的大鼠后代。使用新物体位置测试，我们发现青春期和年轻成年雌性后代的空间记忆受损。青春期和年轻成年后代的识别记忆没有改变。我们还发现 NMDA 受体亚基、NMDA 受体相关支架蛋白和调节 NMDA 受体活性的选定 microRNAs 的表达在后代的内侧前额叶皮层和海马体中发生了多种改变。从后代的内侧前额叶皮层和海马体中获得的细胞外液中鉴定出谷氨酸水平的性别依赖性变化。所得结果表明，母亲在怀孕期间和哺乳期的高脂肪饮食会导致后代出现记忆障碍，并伴有 NMDA 受体表达的改变。
