Effect of sulindac on improving autistic behaviors in rats.
- Author:
Liyan QIN
1
;
Xufang DAI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Autistic Disorder; drug therapy; Disease Models, Animal; Down-Regulation; Female; Glycogen Synthase Kinase 3; metabolism; Glycogen Synthase Kinase 3 beta; Prefrontal Cortex; Pregnancy; Rats; Sulindac; pharmacology; Up-Regulation; Valproic Acid; Wnt Signaling Pathway; beta Catenin; metabolism
- From: Journal of Southern Medical University 2015;35(8):1162-1165
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms.
METHODSAutistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23 days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of β-catenin and phosphorylated Gsk3β in the brain tissues were investigated by Western blotting.
RESULTSCompared with the control rats, the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times. Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats, but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3β downregulation and β-catenin upregulation in the prefrontal lobe, seahorse and cerebellum.
CONCLUSIONSulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway.
