LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats

The present study was designed to investigate the effects of LY294002 on Tourette syndrome (TS) in rats. TS model was induced in rats by DOI (the selective 5-HT2A/2C agonist 1- (2, 5- dimethoxy -4 - iodophenyl) -2- aminopropane). Behavior was assessed by stereotypic score and autonomic activity. Inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in serum and striatum were detected. The protein levels of PI3K/Akt/NF-B in striatum were detected by Western Blot. LY294002 treatment significantly reduced IL-6, IL-1 beta and TNF-alpha in serum and striatum of TS rats, Also, highly expressed P-PI3K, P-Akt, P-NF-kappa Bp65, P-I kappa B alpha in TS rats were restored respectively by LY294002 treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that the protective effect of LY294002 against TS in rat might be associated with the regulation of PI3K/Akt/NF-B pathway.