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患有胎儿酒精谱系障碍的青春期前儿童血清中的神经炎症标志物。

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders.

作者信息

Fiore Marco, Petrella Carla, Coriale Giovanna, Rosso Pamela, Fico Elena, Ralli Massimo, Greco Antonio, De Vincentiis Marco, Minni Antonio, Polimeni Antonella, Vitali Mario, Messina Marisa Patrizia, Ferraguti Giampiero, Tarani Francesca, de Persis Simone, Ceccanti Mauro, Tarani Luigi

机构信息

Institute of Biochemistry and Cell Biology, IBBC-CNR, Rome, Italy.

Centro Riferimento Alcologico Regione Lazio, ASL Roma 1, Rome, Italy.

出版信息

CNS Neurol Disord Drug Targets. 2022;21(9):854-868. doi: 10.2174/1871527320666211201154839.

Abstract

BACKGROUND

Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress.

HYPOTHESIS/OBJECTIVE: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS).

METHODS

Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as Free Oxygen Radicals Test (FORT) and Free Oxygen Radicals Defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated.

RESULTS

We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children.

CONCLUSION

The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

摘要

背景

胎儿酒精谱系障碍(FASD)是孕期饮酒所致损害的表现。胎儿酒精综合征(FAS)作为FASD的极端表现形式,患儿会出现面部畸形和智力发育迟缓。孕期摄入酒精会损害大脑发育,其中包括减少神经营养因子和神经炎症标志物的合成与释放。饮酒还会引发氧化应激。

假设/目的:本研究旨在调查12名诊断为FAS或部分FAS(pFAS)的青春期前FASD男童和女童中神经营养因子、神经炎症和氧化应激之间的潜在关联。

方法

相应地,我们分析了血清中脑源性神经营养因子(BDNF)和神经生长因子(NGF)的水平以及氧化应激情况,即游离氧自由基测试(FORT)和游离氧自由基防御能力(FORD)。此外,还研究了参与神经炎症和氧化过程的炎症介质(白细胞介素-1α、白细胞介素-2、白细胞介素-6、白细胞介素-10、白细胞介素-12、单核细胞趋化蛋白-1、转化生长因子-β和肿瘤坏死因子-α)的血清水平。

结果

我们发现,与健康对照组相比,青春期前FASD儿童的血清中NGF和BDNF水平较低。这些变化与血清中肿瘤坏死因子-α和白细胞介素-1α的含量升高有关。非常有趣的是,尽管FORT水平正常,但FORD却有所升高。此外,我们发现,与男童相比,分析的女童中白细胞介素-1α、白细胞介素-2、白细胞介素-10和白细胞介素-1α1有所增强。

结论

本研究表明,外周神经免疫途径存在失衡,这可作为儿童FASD中所观察到缺陷的早期生物标志物。

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