在大多数哺乳动物物种中,母体营养被认为是大脑生长和成熟的重要组成部分。及时干预合适的营养品将提供长期的健康益处。我们的目标是解开围产期营养不良引起的认知和突触可塑性损伤的分子机制。采用基于膳食营养补充剂的动物模型。我们在怀孕时治疗营养不良的水坝,泌乳,在虾青素(AsX)和二十二碳六烯酸(DHA)的两个时间点,它们的幼崽被用作实验动物。我们通过对幼犬进行成年后的行为测试来评估认知功能。此外,我们评估了海马中与认知功能和突触可塑性相关的基因的表达。我们的结果显示脑源性神经营养因子(BDNF)的下调,神经营养蛋白-3(NT-3),cAMP反应元件结合蛋白(CREB),和解偶联蛋白-2(UCP2)基因在幼鼠出生在他们的成年生活,其中AsX和DHA调节。母亲补充AsX和DHA改善了后代中新型物体识别(NOR)测试和部分诱饵的radial臂迷宫(RAM)任务中营养不足引起的学习障碍。与对照组和AsX-DHA治疗组相比,围产期营养不足组的Synapsin-1和PSD-95的表达在CA1,CA2,CA3和DG降低。AsX和DHA补充上调BDNF,NT-3,CREB,围生期营养不良大鼠的UCP2基因表达,它们参与像Ras这样的细胞内信号级联,PI3K,和PLC。我们的研究结果为神经元分化提供了新的见解,生存,和可塑性,这表明围产期是逆转母亲营养不良导致的后代认知障碍的关键时期。
Maternal nutrition was recognized as a significant part of brain growth and maturation in most mammalian species. Timely intervention with suitable nutraceuticals would provide long-term health benefits. We aim to unravel the molecular mechanisms of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated undernourished dams at their gestational, lactational, and at both the time point with Astaxanthin (AsX) and Docosahexaenoic acid (DHA), and their pups were used as experimental animals. We evaluated the cognitive function by subjecting the pups to behavioral tests in their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and uncoupling protein-2 (UCP2) gene expression in pups born to undernourished dams in their adult life, which AsX and DHA modulated. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) tasks in offspring\'s. The expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control and AsX-DHA treated groups at CA1, CA2, CA3, and DG. AsX and DHA supplementation upregulated BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished rats, which are involved in intracellular signaling cascades like Ras, PI3K, and PLC. The results of our study give new insights into neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing maternal undernutrition-induced cognitive impairment in offspring\'s.