Neuroprotective Effect of Palmatine Against Anti-Epileptic Drug Induced Autism in Wistar Rat Pups.

BACKGROUND

Autism spectrum disorder is a developmental disorder that affects the central nervous system. It is characterized by impaired social interaction and communication, along with patterns of repetitive behaviours. The present study was conducted to evaluate the effect of palmatine in autistic male rat pups.

METHODS

In this study, sodium valproate (400 mg/kg) was injected by subcutaneous route on the 13th gestational day to Wistar female rats to induce autism-like symptoms in their pups. Palmatine (0.25, 0.5 and 1 mg/kg) was orally administered for 35 consecutive days (from postnatal day 24 to 58) to autistic male pups. The pups were subjected to various behavioural tests like the tail immersion test, actophotometer, tail suspension test, elevated zero maze, social interaction test and Morris water maze. One hour after the administration of drugs on postnatal day 58, animals were sacrificed by cervical dislocation followed by the collection of brain and blood samples which were used for estimations of biochemical parameters. Histopathological studies on the cerebellum part of the brain of pups were also carried out.

RESULTS

The results demonstrated a significant decrease in body weight; a significant increase in eye opening time; and significant impairment of motor coordination (as indicated by a significant increase in negative geotaxis score) in male pups, indicating the induction of autism in them. There was a significant increase in pain threshold, hyperlocomotion, depressive and anxious behaviours, impairment of learning and memory and impairment of social interaction in autistic pups. There was a significant increase in oxidative stress (indicated by elevated malondialdehyde and nitrite levels along with a decrease in catalase activity and GSH level), acetylcholinesterase and MAO-A activities in the brain of autistic pups. There was also an increase in plasma corticosterone levels in autistic pups. Palmatine significantly reversed behavioural, biochemical and histopathological alterations in autistic male rat pups.

CONCLUSION

It was concluded that palmatine produced neuroprotective activity in autistic male rat pups possibly through amelioration of brain oxidative stress, inhibition of acetylcholinesterase and MAO-A activities and decrease of plasma corticosterone concentration.