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产前地塞米松治疗及断奶后适度果糖摄入对成年雄性Wistar大鼠后代突触可塑性及行为的影响

Effects of Prenatal Dexamethasone Treatment and Post-Weaning Moderate Fructose Intake on Synaptic Plasticity and Behavior in Adult Male Wistar Rat Offspring.

作者信息

Ignjatović Đurđica, Nestorović Nataša, Tomić Mirko, Ristić Nataša, Veličković Nataša, Perović Milka, Manojlović-Stojanoski Milica

机构信息

Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.

Department of Cytology, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.

出版信息

Biology (Basel). 2024 Jul 19;13(7):547. doi: 10.3390/biology13070547.

DOI:10.3390/biology13070547
PMID:39056739
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11274266/
Abstract

Early-life glucocorticoid overexposure induces diverse neurodevelopmental outcomes regarding stress reactivity and cognition. Increased fructose consumption has also been associated with alterations in cognitive capacity and behavior. The present study investigated the effects of prenatal dexamethasone exposure on synaptic plasticity, locomotion, anxiety, and recognition memory in adult male Wistar rat offspring, and whether these effects are potentiated by postnatal fructose consumption. Pregnant female rats were treated with dexamethasone during late gestation and male offspring were supplemented with a moderate dose of fructose. Recognition memory, locomotion, and anxiety-like behavior were assessed using a novel object recognition test, open-field test, and elevated plus maze, respectively. Hippocampal synaptic plasticity was estimated by the levels of growth-associated protein 43 (GAP-43), synaptophysin, postsynaptic density protein 95, calcium/calmodulin-dependent kinase IIα, and their activating phosphorylations. Additionally, protein levels of the glucocorticoid receptor (GR) and its transcriptionally active phosphorylated form were evaluated. Prenatal dexamethasone treatment induced an anxiolytic-like effect, stimulation of exploratory behavior, and novelty preference associated with an increase in GR and GAP-43 protein levels in the hippocampus. Fructose overconsumption after weaning did not modify the effects of prenatal glucocorticoid exposure. Applied prenatal dexamethasone treatment may induce changes in reactions to novel situations in male Wistar rats.

摘要

生命早期糖皮质激素过度暴露会导致与应激反应性和认知相关的多种神经发育结果。果糖摄入量增加也与认知能力和行为的改变有关。本研究调查了产前地塞米松暴露对成年雄性Wistar大鼠后代的突触可塑性、运动、焦虑和识别记忆的影响,以及这些影响是否会因产后果糖摄入而增强。妊娠晚期对怀孕的雌性大鼠进行地塞米松处理,并对雄性后代补充中等剂量的果糖。分别使用新颖物体识别测试、旷场测试和高架十字迷宫评估识别记忆、运动和焦虑样行为。通过生长相关蛋白43(GAP-43)、突触素、突触后致密蛋白95、钙/钙调蛋白依赖性激酶IIα的水平及其激活磷酸化来估计海马突触可塑性。此外,评估了糖皮质激素受体(GR)及其转录活性磷酸化形式的蛋白质水平。产前地塞米松处理诱导了类似抗焦虑的作用、探索行为的刺激以及与海马中GR和GAP-43蛋白水平增加相关的新奇偏好。断奶后果糖过度摄入并未改变产前糖皮质激素暴露的影响。应用产前地塞米松处理可能会诱导雄性Wistar大鼠对新情况的反应发生变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/e63c3ccb68bd/biology-13-00547-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/79761d2155a5/biology-13-00547-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/128d027b6e19/biology-13-00547-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/58f47b3b4a59/biology-13-00547-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/e63c3ccb68bd/biology-13-00547-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/79761d2155a5/biology-13-00547-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/128d027b6e19/biology-13-00547-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/58f47b3b4a59/biology-13-00547-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda9/11274266/e63c3ccb68bd/biology-13-00547-g004.jpg

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本文引用的文献

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Antenatal steroids: benefits, risks, and new insights.产前类固醇:益处、风险和新见解。
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Early life exposure to high fructose diet induces metabolic dysregulation associated with sex-specific cognitive impairment in adolescent rats.
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