Protection by tyrosine kinase inhibitor, tyrphostin AG126, through the suppression of IL-17A, RORγt, and T-bet signaling, in the BTBR mouse model of autism

Brain Research Bulletin
Sheikh Fayaz AhmadSabry M Attia

Abstract

Autism spectrum disorder (ASD) is an extremely predominant neurodevelopmental disorder expressed as impairment in reciprocal social interaction along with repetitive, restricted, and stereotyped behaviors. The protein tyrosine kinase inhibitor, tyrphostin AG126 (AG126), regulates the expression of several genes that play an important role in the development of neuroinflammatory disorders. Here, we investigate the possible effects of AG126 (5 mg/kg daily through intraperitoneal injection) on self-grooming, marble burying, and hot plate test results in BTBR T + Itpr3tf/J mice (BTBR is a model of autism). We also explore the effects of AG126 administration on IL-17 A, RORγt, T-bet, and IFN-γ production in CD4+ T cells and on CCR6+ chemokine receptors in splenic cells. We further investigated the effect of AG126 administration on the mRNA and protein expression of IL-17 A, RORγt, T-bet, IFN-γ, and NF-κB in the brain tissue. Our results demonstrate that treatment of BTBR mice with AG126 reduced repetitive self-grooming scores and lowered hot plate sensitivity potentials. Furthermore, AG126 administration also caused a substantial reduction of IL-17 A, RORγt, T-bet, and IFN-γ production in CD4+ T cells and on CCR6+ chemokine receptor...Continue Reading

Citations

May 22, 2020·Neuroscience and Biobehavioral Reviews·Lidia BravoEsther Berrocoso
Jul 10, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Júlio Santos-TerraCarmem Gottfried

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