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母体高脂饮食会增加成年后代的快感缺失行为,并调节海马体中Mash1和脑源性神经营养因子(BDNF)的表达。

Maternal high-fat diet increases anhedonic behavior and modulates hippocampal Mash1 and BDNF expression in adult offspring.

作者信息

Curi Haidar Tafner, Dias Clarissa Tavares, da Luz Camargo Maria Laura Monteiro, Dos Santos Gomez Paula, Gomes Moisés Felipe Pereira, Beserra-Filho José Ivo Araujo, Medeiros Alessandra, Ribeiro Alessandra Mussi, Simabuco Fernando Moreira, Lambertucci Rafael Herling, Mendes-da-Silva Cristiano

机构信息

Laboratory of Neuroscience and Nutrition, Department of Biosciences, Federal University of Sao Paulo/UNIFESP, Santos, SP, Brazil.

Laboratory of Experimental Physical Training, Department of Biosciences, Federal University of Sao Paulo (UNIFESP), Santos, SP, Brazil.

出版信息

Neurosci Lett. 2021 Nov 1;764:136239. doi: 10.1016/j.neulet.2021.136239. Epub 2021 Sep 10.

Abstract

BACKGROUND

The consumption of a high-fat diet (HFD) during pregnancy and perinatal periods can lead to long-term effects in the offspring central nervous system, affecting pathways related to neurogenesis and behavior, and increasing predispositions to depressive and anxiety-like behaviors. Thus, this study aimed to investigate the effects of a maternal HFD on the hippocampi of adult offspring and behaviors related to anxiety and depression.

METHODS

The protein and mRNA expression of the brain-derived neurotrophic factor (BDNF), Mash1, Notch1, Hes5, serotonin transporter (SERT), 5-HT1A serotonergic receptor (5-HT1A), tryptophan hydroxylase 2 (TPH2, key enzyme of serotonin synthesis), JNK and pJNK were analyzed in the hippocampi of male Swiss mice. Hippocampal serotonin levels were measured using ELISA. The lipid peroxidation, total oxidant status, total antioxidant status, and GSH/GSSG were evaluated as oxidative stress measures. For the behavioral analysis, the open field, elevated plus maze, and sucrose preference tests were used.

RESULTS

Maternal HFD led to increased body weight in dams and their offspring, as well as altered body composition and LDL levels in the offspring. There were no alterations in oxidative stress or JNK phosphorylation. Hippocampal Mash1 and BDNF expression were altered in HFD offspring. The HFD offspring exhibited anhedonic behavior.

CONCLUSION

These findings suggest that maternal HFD leads to long-term alterations in the offspring's neurotrophic systems, impairing their behavior.

摘要

背景

孕期和围产期摄入高脂饮食(HFD)会对后代中枢神经系统产生长期影响,影响与神经发生和行为相关的通路,并增加抑郁和焦虑样行为的易感性。因此,本研究旨在探讨母体高脂饮食对成年后代海马体以及与焦虑和抑郁相关行为的影响。

方法

分析雄性瑞士小鼠海马体中脑源性神经营养因子(BDNF)、Mash1、Notch1、Hes5、血清素转运体(SERT)、5-HT1A血清素能受体(5-HT1A)、色氨酸羟化酶2(TPH2,血清素合成的关键酶)、JNK和pJNK的蛋白质和mRNA表达。使用酶联免疫吸附测定法测量海马体血清素水平。评估脂质过氧化、总氧化剂状态、总抗氧化剂状态和GSH/GSSG作为氧化应激指标。行为分析采用旷场试验、高架十字迷宫试验和蔗糖偏好试验。

结果

母体高脂饮食导致母鼠及其后代体重增加,以及后代身体成分和低密度脂蛋白水平改变。氧化应激或JNK磷酸化没有变化。高脂饮食后代海马体中Mash1和BDNF表达发生改变。高脂饮食后代表现出快感缺失行为。

结论

这些发现表明,母体高脂饮食会导致后代神经营养系统的长期改变,损害其行为。

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