Aflatoxin B 1 exposure deteriorates immune abnormalities in a BTBR T + Itpr3 tf /J mouse model of autism by increasing inflammatory mediators' production in CD19-expressing cells

• Published in: Journal of neuroimmunology 2024-06, Vol.391, p.578365
• Main Authors: Almanaa, Taghreed N, Alwetaid, Mohammad Y, Bakheet, Saleh A, Attia, Sabry M, Ansari, Mushtaq A, Nadeem, Ahmed, Ahmad, Sheikh F
• Format: Article
• Language: English
• Subjects: Aflatoxin B1 - toxicity; Animals; Antigens, CD19 - metabolism; Autistic Disorder - chemically induced; Autistic Disorder - immunology; Autistic Disorder - metabolism; Disease Models, Animal; Inflammation Mediators - metabolism; Male; Mice; Mice, Transgenic
• ISSN: 1872-8421
• DOI: 10.1016/j.jneuroim.2024.578365

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 B (AFB ) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB results in neurological problems. The BTBR T Itpr3 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 AFB in BTBR mice. This work aimed to examine the effects of AFB 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 AFB 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 AFB 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 AFB 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 AFB worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.