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孕期、哺乳期和成年期的限制和高脂饮食改变了雌性小鼠及其成年后代多巴胺能系统相关基因的表达。

Restriction and hyperlipidic diets during pregnancy, lactation and adult life modified the expression of dopaminergic system related genes both in female mice and their adult offspring.

机构信息

Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245 - Porto Alegre, Rio Grande do Sul, CEP 90050-170, Brazil.

Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245 - Porto Alegre, Rio Grande do Sul, CEP 90050-170, Brazil.

出版信息

Brain Res Bull. 2020 Sep;162:245-252. doi: 10.1016/j.brainresbull.2020.06.019. Epub 2020 Jun 30.

Abstract

The neurocircuitry underlying hunger, satiety, motivation to eat and food reward is complex, however a lot of mechanisms are still unknown. Two main cerebral areas are responsible for controlling feeding through hunger and food reward: the hypothalamus (HPT) and the ventral tegmental area (VTA), respectively. The dopaminergic system modulates both these areas and is essential to control food ingestion. Therefore, we aim to evaluate the effects of restrictive and hyperlipidic diets during pregnancy, lactation and during adult life of the offspring, on the expression of dopaminergic system genes in VTA and HPT of mice dams and their adult male offspring. We also measured diets' effect in locomotor activity in the open field (OF) test. Female mice were divided into control (CONT), restriction (RD) and hyperlipidic (HD) dietary groups, and mated with isogenic male mice. On the 9th postpartum day (PPD), dams were tested in the OF, and on the 22nd PPD cerebral areas were collected. After weaning, the offspring also were divided into one of three diet groups, independently of the diets provided to their dams. In the 80th PPD, the offspring was tested in the OF, and at 100th PPD, VTA and HPT were collected. Gene expression was analyzed by quantitative reverse transcription real-time polymerase chain reaction. The correlation between gene expression and locomotor activity was also assessed. In dams' VTA, both diets upregulated the expression of Th, Slc6a3/Dat1, Drd1 and Drd2 genes. In opposition, in the offspring the maternal diet was associated with a reduction in Th and Ddc gene expression. In the HPT, mice dams that received restriction or hyperlipidic diets had increased Th mRNA levels, but reduced the expression of Drd4 gene. The offspring diet had no effect on the expression of the studied genes in their adult lives. Both diets increased mice dam's locomotion in the OF, however none of them altered the offspring locomotor activity. We detected a positive correlation between the duration of total locomotion in the OF and Slc6a3/Dat1 gene expression in VTA of mice dams. In the HPT, a negative correlation of locomotion and Drd4 mRNA levels, and a positive correlation with Th gene expression was observed. Our results show that restriction and hyperlipidic diets alter mice dams' locomotor activity in the OF and modify the expression of dopaminergic system genes in VTA and HPT of mice dams and in VTA of the offspring.

摘要

控制饥饿、饱腹感、进食动机和食物奖励的神经回路非常复杂,但仍有许多机制尚不清楚。两个主要的大脑区域负责通过饥饿和食物奖励来控制进食:下丘脑(HPT)和腹侧被盖区(VTA)。多巴胺能系统调节这两个区域,对于控制食物摄入至关重要。因此,我们旨在评估限制和高脂饮食在怀孕、哺乳期和成年期对子代小鼠母鼠 VTA 和 HPT 中多巴胺能系统基因表达的影响,以及对母鼠和成年雄性子代在旷场(OF)测试中的运动活性的影响。我们还测量了饮食对旷场(OF)测试中运动活性的影响。雌性小鼠分为对照组(CONT)、限制组(RD)和高脂组(HD),并与同基因雄性小鼠交配。在产后第 9 天(PPD),母鼠在旷场中进行测试,在产后第 22 天收集大脑区域。断奶后,子代也分为三组饮食组之一,与母鼠提供的饮食无关。在产后第 80 天,子代在旷场中进行测试,在产后第 100 天,收集 VTA 和 HPT。通过定量逆转录实时聚合酶链反应分析基因表达。还评估了基因表达与运动活性之间的相关性。在母鼠的 VTA 中,两种饮食均上调了 Th、Slc6a3/Dat1、Drd1 和 Drd2 基因的表达。相反,在子代中,母体饮食与 Th 和 Ddc 基因表达减少有关。在 HPT 中,接受限制或高脂饮食的母鼠 Th mRNA 水平升高,但 Drd4 基因表达降低。子代饮食在成年期对研究基因的表达没有影响。两种饮食都增加了母鼠在旷场中的运动,但都没有改变子代的运动活性。我们检测到母鼠旷场中总运动时间与 VTA 中 Slc6a3/Dat1 基因表达之间存在正相关。在 HPT 中,观察到运动与 Drd4 mRNA 水平呈负相关,与 Th 基因表达呈正相关。我们的研究结果表明,限制和高脂饮食改变了母鼠在旷场中的运动活性,并改变了母鼠 VTA 和 HPT 以及子代 VTA 中多巴胺能系统基因的表达。

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