Ursolic acid enhances social behavior and modulates Th1, Th17, and T regulatory cell-related transcription factor signaling in the BTBR TItpr3/J mouse model of autism.

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by unusual social interactions, limited speech, and repetitive behaviors or hobbies. The BTBR TItpr3J (BTBR) inbred mice are commonly used as a model for ASD because they display many genetic traits associated with autism. Ursolic acid, a naturally occurring compound found in several plants, has shown promise as a treatment for various inflammatory disorders and related experimental models. This study aimed to explore the potential effects of ursolic acid on self-grooming, marble burying, and social behaviors in BTBR mice. We examined how ursolic acid affects the expression of Th1 (IFN-γ, TNF-α, STAT1, STAT4, and T-bet), Th17 (IL-17, RORγt, and STAT3), and T regulatory (Treg; IL-10, TGF-β1, and Foxp3) markers in CD4T cells within the spleens of BTBR and C57BL/6 mice. Additionally, we assessed the impact of ursolic acid on brain mRNA levels of IFN-γ, TNF-α, STAT1, STAT4, T-bet, IL-17, RORγ, STAT3, IL-10, TGF-β1, and Foxp3. Treatment with ursolic acid significantly affected behavioral issues in BTBR mice. In these animals, ursolic acid reduced the levels of Th1 and Th17 cells while increasing the levels of Treg cells. Furthermore, it decreased the expression of Th1 and Th17 mRNA and increased the expression of Treg-related mRNA in the brain. Our findings suggest that, due to its anti-inflammatory properties, ursolic acid may be a beneficial treatment for behavioral impairments in BTBR mice.