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长期暴露于草甘膦基除草剂的幼鼠海马体和前额叶皮质的神经糖组改变

Neuroglycome alterations of hippocampus and prefrontal cortex of juvenile rats chronically exposed to glyphosate-based herbicide.

作者信息

Solomon Joy, Gutierrez-Reyes Cristian D, Chávez-Reyes Jesús, Onigbinde Sherifdeen, Marichal-Cancino Bruno A, López-Lariz Carlos H, Beck Mia, Mechref Yehia

机构信息

Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, United States.

Department of Physiology and Pharmacology, Center of Basic Sciences, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico.

出版信息

Front Neurosci. 2024 Aug 21;18:1442772. doi: 10.3389/fnins.2024.1442772. eCollection 2024.

Abstract

INTRODUCTION

Glyphosate-based herbicides (GBHs) have been shown to have significant neurotoxic effects, affecting both the structure and function of the brain, and potentially contributing to the development of neurodegenerative disorders. Despite the known importance of glycosylation in disease progression, the glycome profile of systems exposed to GBH has not been thoroughly investigated.

METHODS

In this study, we conducted a comprehensive glycomic profiling using LC-MS/MS, on the hippocampus and prefrontal cortex (PFC) of juvenile rats exposed to GBH orally, aiming to identify glyco-signature aberrations after herbicide exposure.

RESULTS

We observed changes in the glycome profile, particularly in fucosylated, high mannose, and sialofucosylated N-glycans, which may be triggered by GBH exposure. Moreover, we found major significant differences in the N-glycan profiles between the GBH-exposed group and the control group when analyzing each gender independently, in contrast to the analysis that included both genders. Notably, gender differences in the behavioral test of object recognition showed a decreased performance in female animals exposed to GBH compared to controls ( < 0.05), while normal behavior was recorded in GBH-exposed male rats ( > 0.05).

CONCLUSION

These findings suggest that glycans may play a role in the neurotoxic effect caused by GBH. The result suggests that gender variation may influence the response to GBH exposure, with potential implications for disease progression and specifically the neurotoxic effects of GBHs. Understanding these gender-specific responses could enhance knowledge of the mechanisms underlying GBH-induced toxicity and its impact on brain health. Overall, our study represents the first detailed analysis of N-glycome profiles in the hippocampus and PFC of rats chronically exposed to GBH. The observed alterations in the expression of N-glycan structures suggest a potential neurotoxic effect associated with chronic GBH exposure, highlighting the importance of further research in this area.

摘要

引言

基于草甘膦的除草剂(GBHs)已被证明具有显著的神经毒性作用,会影响大脑的结构和功能,并可能导致神经退行性疾病的发展。尽管糖基化在疾病进展中的重要性已为人所知,但暴露于GBH的系统的糖组学特征尚未得到充分研究。

方法

在本研究中,我们使用液相色谱-串联质谱(LC-MS/MS)对口服GBH的幼年大鼠的海马体和前额叶皮质(PFC)进行了全面的糖组学分析,旨在识别除草剂暴露后的糖基特征异常。

结果

我们观察到糖组学特征发生了变化,特别是在岩藻糖基化、高甘露糖和唾液酸岩藻糖基化的N-聚糖中,这些变化可能是由GBH暴露引发的。此外,与包含两性的分析相比,在独立分析每个性别时,我们发现GBH暴露组和对照组之间的N-聚糖谱存在重大显著差异。值得注意的是,在物体识别行为测试中,与对照组相比,暴露于GBH的雌性动物表现下降(<0.05),而暴露于GBH的雄性大鼠行为正常(>0.05)。

结论

这些发现表明聚糖可能在GBH引起的神经毒性作用中发挥作用。结果表明性别差异可能会影响对GBH暴露的反应,对疾病进展特别是GBHs的神经毒性作用具有潜在影响。了解这些性别特异性反应可以增强对GBH诱导毒性的潜在机制及其对大脑健康影响的认识。总体而言,我们的研究代表了对长期暴露于GBH的大鼠海马体和PFC中N-糖组谱的首次详细分析。观察到的N-聚糖结构表达变化表明与慢性GBH暴露相关的潜在神经毒性作用,突出了该领域进一步研究的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e13/11371619/235c03c8d7dc/fnins-18-1442772-g001.jpg

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