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黄曲霉毒素B暴露加剧BTBR T Itpr3/J小鼠模型中趋化因子受体的表达,揭示自闭症谱系障碍的相关见解:聚焦于脑和脾脏。

Aflatoxin B exposure exacerbates chemokine receptor expression in the BTBR T Itpr3/J Mouse Model, unveiling insights into autism spectrum disorder: A focus on brain and spleen.

作者信息

Alwetaid Mohammad Y, Almanaa Taghreed N, Bakheet Saleh A, Ansari Mushtaq A, Nadeem Ahmed, Attia Sabry M, Hussein Marwa H, Attia Mohamed S M, Ahmad Sheikh F

机构信息

Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Reprod Toxicol. 2024 Jun;126:108599. doi: 10.1016/j.reprotox.2024.108599. Epub 2024 Apr 26.

DOI:10.1016/j.reprotox.2024.108599
PMID:38679149
Abstract

OBJECTIVE

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant difficulties in social interaction, communication, and repeated stereotypic behaviour. Aflatoxin B (AFB) is the most potent and well-known mycotoxin in various food sources. Despite its propensity to generate significant biochemical and structural changes in human and animal tissues, the influence of AFB on ASD has yet to be thoroughly studied. Mounting evidence indicates that chemokine receptors play a crucial function in the central nervous system and are implicated in developing several neuroinflammatory disorders. Chemokine receptors in individuals with ASD were elevated in the anterior cingulate gyrus astrocytes, cerebellum, and brain.

METHODS

The BTBR TItpr3J (BTBR) mice are inbred strains that exhibit strong and consistently observed deficits in social interactions, characterized by excessive self-grooming and limited vocalization in social contexts. We examined the impact of AFB on CCR3-, CCR7-, CCR9-, CXCR3-, CXCR4-, and CXCR6-expressing I-A/I-E cells in the spleen of the BTBR mouse model of autism. We evaluated the mRNA levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 chemokine receptors in the brain.

RESULTS

The exposure to AFB in BTBR mice resulted in a significant rise in the number of I-A/I-ECCR3, I-A/I-ECCR7, I-A/I-ECCR9, I-A/I-ECXCR3, I-A/I-ECXCR4, and I-A/I-ECXCR6 cells. Furthermore, exposure to AFB increased mRNA expression levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 in the brain.

CONCLUSIONS

These findings highlight that AFB exposure increases the expression of chemokine receptors in BTBR mice, indicating the necessity for further research into AFB's role in the development of ASD.

摘要

目的

自闭症谱系障碍(ASD)是一种神经发育疾病,其特征为社交互动、沟通及重复刻板行为方面存在显著困难。黄曲霉毒素B(AFB)是各类食物来源中最具毒性且最为人熟知的霉菌毒素。尽管它易于在人和动物组织中引发显著的生化及结构变化,但AFB对ASD的影响尚未得到充分研究。越来越多的证据表明,趋化因子受体在中枢神经系统中发挥关键作用,并与多种神经炎症性疾病的发生有关。ASD患者前扣带回皮质星形胶质细胞、小脑及大脑中的趋化因子受体水平升高。

方法

BTBR TItpr3J(BTBR)小鼠是近交系,表现出强烈且持续存在的社交互动缺陷,其特征为过度自我梳理以及在社交情境中发声受限。我们研究了AFB对自闭症BTBR小鼠模型脾脏中表达CCR3、CCR7、CCR9、CXCR3、CXCR4和CXCR6的I-A/I-E细胞的影响。我们评估了大脑中CCR3、CCR7、CCR9、CXCR3、CXCR4和CXCR6趋化因子受体的mRNA水平。

结果

BTBR小鼠接触AFB后,I-A/I-E CCR3、I-A/I-E CCR7、I-A/I-E CCR9、I-A/I-E CXCR3、I-A/I-E CXCR4和I-A/I-E CXCR6细胞数量显著增加。此外,接触AFB会增加大脑中CCR3、CCR7、CCR9、CXCR3、CXCR4和CXCR6的mRNA表达水平。

结论

这些发现表明,AFB暴露会增加BTBR小鼠趋化因子受体的表达,这表明有必要进一步研究AFB在ASD发病过程中的作用。

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