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Effects of chronic unpredictable mild stress induced prenatal stress on neurodevelopment of neonates: Role of GSK-3β.

ABSTRACT: Prenatal stress (PNS) has gained attention with regard to its impact on hippocampal neurogenesis in neonates which serves as a risk factor for postnatal neurodevelopmental deficits. Evidences from animal models have suggested that depression responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal response via cortisol, is responsible for critical neurodevelopmental deficits in the offspring which is transduced due to gestational stress. But knowledge in the area of assessing the effects of maternal chronic unpredictable mild stress (CUMS) on neurogenesis and expression of some key signaling molecules in the offsprings are limited. We have used Wistar rats to induce PNS in offsprings by maternal CUMS during pregnancy. Prefrontal cortex (PFC) and hippocampus were assessed for biomarkers of oxidative stress, neurogenesis, neurodevelopmental signaling molecules and DNA damage in the male Wister offsprings. Our investigations resulted in sufficient evidences which prove how maternal psychological stress has widespread effect on the fetal outcomes via major physiological alteration in the antioxidant levels, neurogenesis, signaling molecules and DNA damage. PNS leads to the upregulation of GSK-3β which in turn inhibited mRNA and protein expressions of sonic hedgehog (SHH), β-catenin, Notch and brain derived neurotrophic factor (BDNF). The study explored multifaceted signaling molecules especially, GSK-3β responsible for crosstalks between different neurodevelopmental molecules like SHH, Notch, BDNF and β-catenin affecting neurodevelopment of the offsprings due to PNS.

SUBMITTER: Fatima M

PROVIDER: S-EPMC6361942 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:It is known that bioenergetics of aerobic and resistance exercise are not the same but both can effectively improve depression. However, it is not clear whether and how different types of exercise can influence depression through the same metabolic regulatory system. Metabolomics provides a way to study the correlation between metabolites and changes in exercise and/or diseases through the quantitative analysis of all metabolites in the organism. The objective of this study was to investigate the effects of aerobic and resistance training on urinary metabolites by metabolomics analysis in a rodent model of depression. METHODS:Male Sprague-Dawley rats were given chronic unpredictable mild stress (CUMS) for eight weeks. The validity of the modeling was assessed by behavioral indices. After four weeks of CUMS, the rats that developed depression were randomly divided into a depression control group, an aerobic training group and a resistance training group. There was also a normal control group. From week 5, the rats in the exercise groups were trained for 30 min per day, five days per week, for four weeks. The urine samples were collected pre and post the training program, and analyzed by proton nuclear magnetic resonance (1H-NMR) spectroscopy. RESULTS:Both types of training improved depression-like behavior in CUMS rats. Compared with normal control, 21 potential biomarkers were identified in the urine of CUMS rats, mainly involved in energy, amino acids and intestinal microbial metabolic pathways. Common responses to the training were found in the two exercise groups that the levels of glutamine, acetone and creatine were significantly recalled (all P<0.05) Aerobic training also resulted in changes in pyruvate and trigonelline, while resistance training modified ?-Oxoglutarate, citric acid, and trimethylamine oxide (all P<0.05). CONCLUSIONS:Aerobic and resistance training resulted in common effects on the metabolic pathways of alanine-aspartate-glutamate, TCA cycle, and butyric acid. Aerobic training also had effects on glycolysis or gluconeogenesis and pyruvate metabolism, while resistance training had additional effect on intestinal microbial metabolism.

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Effects of chronic unpredictable mild stress induced prenatal stress on neurodevelopment of neonates: Role of GSK-3β.

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