Thymol improves autism-like behaviour in VPA-induced ASD rats through the Pin1/p38 MAPK pathway

Inflammation plays an essential role in the pathogenesis of autism spectrum disorder (ASD). Thymol is a bioactive monoterpene isolated from Thymus vulgaris that has anti-inflammatory properties and is helpful in neurodevelopmental disorders. The purpose of this study was to investigate the effects of thymol on autism-like behaviours in rats with VPA-induced ASD and to assess the related molecular mechanisms. In the prefrontal cortex (PFC) of the valproic acid (VPA)-exposed rat model, the levels of PIN1, phosphorylated p38 MAPK, interleukin-1β (IL-1β) and tumour necrosis factor (TNF)-α, were increased, and the levels of PSD95 and synaptophysin (SYP) decreased. After thymol treatment (30 mg/kg), the VPA-induced autism-like behaviours were alleviated. Moreover, thymol also rescued the dysregulated levels of PIN1, phosphorylated p38 MAPK, IL-1β, TNF-α, PSD95, and SYP. In addition, immunofluorescence experiments showed that thymol treatment decreased the correlation between PIN1 and phosphorylated p38 MAPK. Mechanistically, PIN1 knockdown by RNA interference confirmed that PIN1 promotes inflammation via phosphorylation of p38 MAPK in the VPA exposure rat model. In conclusion, thymol improved autism-like behaviours in VPA-induced ASD rats by reducing inflammation and improving neurodevelopment. This effect was mediated by the PIN1/p38 MAPK pathway. These results experimentally provide the potential for thymol in new therapeutic avenues for autism.

Autism spectrum disorders; Inflammation; P38 MAPK; Pin1; Thymol; Valproic acid.