Aflatoxin B1 exposure exacerbates chemokine receptor expression in the BTBR T+ Itpr3tf/J Mouse Model, unveiling insights into autism spectrum disorder: A focus on brain and spleen

Abstract

Objective

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant difficulties in social interaction, communication, and repeated stereotypic behaviour. Aflatoxin B₁ (AFB₁) 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 AFB₁ 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 T⁺Itpr3^tf/J (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 AFB₁ 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 AFB₁ in BTBR mice resulted in a significant rise in the number of 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⁺, and I-A/I-E⁺CXCR6⁺ cells. Furthermore, exposure to AFB₁ increased mRNA expression levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 in the brain.

Conclusions

These findings highlight that AFB₁ exposure increases the expression of chemokine receptors in BTBR mice, indicating the necessity for further research into AFB₁'s role in the development of ASD.