[Effect of sulindac on improving autistic behaviors in rats].
OBJECTIVE
To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms.


METHODS
Autistic 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.


RESULTS
Compared 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.


CONCLUSIONS
Sulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway.
hongqing Key Laboratory of Psychological Diagnosis and Educational Technology for Children with Special Needs, Chongqing 400047, China. E-mail: xufangd@aliyun.com.
Liyan
L
Qin
Xufang
X
Dai
D000818:Animals; D001321:Autistic Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D017397:Prefrontal Cortex; D011247:Pregnancy; D051381:Rats; D013467:Sulindac / Q000494:pharmacology*; D015854:Up-Regulation; D014635:Valproic Acid; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
C495268:Ctnnb1 protein, rat; D051176:beta Catenin; D013467:Sulindac; D014635:Valproic Acid; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3