Aflatoxin B1 exposure deteriorates immune abnormalities in a BTBR T+ Itpr3tf/J mouse model of autism by increasing inflammatory mediators' production in CD19-expressing cells

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B₁ (AFB₁) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB₁ is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB₁ results in neurological problems. The BTBR T⁺ Itpr3^tf/J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB₁ in BTBR mice. This work aimed to examine the effects of AFB₁ on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19⁺ B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB₁ exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB₁ in the BTBR group exhibited a substantial increase in the presence of CD19⁺Notch-1⁺, CD19⁺IL-6⁺, CD19⁺MCP-1⁺, CD19⁺iNOS⁺, CD19⁺GM-CSF⁺, and CD19⁺NF-κB p65⁺ compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB₁ to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB₁ worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.