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Prenatal ethanol exposure enhances the susceptibility to depressive behavior of adult offspring rats fed a high?fat diet by affecting BDNF?associated pathway.

ABSTRACT: Epidemiological studies have shown that exposure to ethanol during pregnancy can result in an increased risk for depression in offspring. A 'brain?derived neurotrophic factor (BDNF) hypothesis' has been proposed to help explain the pathogenic mechanism of depression. This study was designed to verify the enhanced susceptibility to depression in prenatal ethanol exposure (PEE) offspring rats and explore possible intrauterine programming mechanisms related to the BDNF signaling pathway. Pregnant rats were intragastrically administrated ethanol (4 g/kg/day) from gestational day 11 until term delivery. All offspring rats were given a high?fat diet after weaning. Then the behavior tests, including sucrose preference test and open field test, were performed to adult offspring rats. The histomorphology of hippocampus was examined, and the expression of genes related to the BDNF signaling pathway was detected in the hippocampus of PEE offspring. The PEE female adult offspring rats showed depression?like behavior, with obvious morphological injury in hippocampus. Additionally, the mRNA expression levels of glucocorticoid receptor (GR) and BDNF pathway?associated genes were changed in hippocampus. Multigene RT?qPCR also revealed that the mRNA expression levels for BDNF pathway?associated genes and synaptic plasticity genes were decreased in the hippocampus of fetal offspring rats in the PEE group. The underlying mechanism involves an increased GR expression that constantly suppresses the BDNF signaling pathway, and aggravates the functional insult to the hippocampus, resulting in an increased susceptibility to depression among PEE female adult offspring rats. Results of the present study provide theoretical and experimental evidence that can be used for the early prevention and treatment of depression.

SUBMITTER: Yu Y

PROVIDER: S-EPMC6984802 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Prenatal ethanol exposure enhances the susceptibility to depressive behavior of adult offspring rats fed a high‑fat diet by affecting BDNF‑associated pathway.

Yu Ying Y Xu Dan D Cheng Siyuan S Zhang Li L Shi Zhaokun Z Qin Jun J Zhang Zhaohui Z Wang Hui H

International journal of molecular medicine 20191219 2

Epidemiological studies have shown that exposure to ethanol during pregnancy can result in an increased risk for depression in offspring. A 'brain‑derived neurotrophic factor (BDNF) hypothesis' has been proposed to help explain the pathogenic mechanism of depression. This study was designed to verify the enhanced susceptibility to depression in prenatal ethanol exposure (PEE) offspring rats and explore possible intrauterine programming mechanisms related to the BDNF signaling pathway. Pregnant r ...[more]

PMID: 31894308

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Project description:BackgroundCombined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated.MethodsFemale mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring.ResultsHFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho β, and its downstream targets, proliferator-activated receptor-γ co-activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring.ConclusionsLeucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.

Dataset Information

Prenatal ethanol exposure enhances the susceptibility to depressive behavior of adult offspring rats fed a high?fat diet by affecting BDNF?associated pathway.

Publications

Prenatal ethanol exposure enhances the susceptibility to depressive behavior of adult offspring rats fed a high‑fat diet by affecting BDNF‑associated pathway.

Similar Datasets

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