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Neuroprotective Effect of Palmatine Against Anti-Epileptic Drug Induced Autism in Wistar Rat Pups
Kulwant Singh1, Dinesh Dhingra1
1Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India.
Insights
Palmatine demonstrated neuroprotective effects in male rat pups with autism-like symptoms. This natural compound reversed behavioral and biochemical changes, suggesting potential therapeutic benefits for autism spectrum disorder.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits, communication impairments, and repetitive behaviors.
- Animal models, such as those induced by sodium valproate, are crucial for understanding ASD pathophysiology and testing potential interventions.
- Palmatine, a natural alkaloid, was investigated for its effects on autism-like symptoms in a rat model.
Purpose of the Study:
- To evaluate the efficacy of palmatine in ameliorating autism-like symptoms in male rat pups.
- To investigate the neuroprotective mechanisms of palmatine, including its impact on oxidative stress and neurotransmitter activity.
Main Methods:
- Autism-like symptoms were induced in Wistar rat pups via subcutaneous injection of sodium valproate on the 13th gestational day.
- Palmatine was administered orally to autistic male pups from postnatal day 24 to 58.
- Behavioral tests, biochemical analyses (oxidative stress markers, enzyme activities), and histopathological examinations were performed.
Main Results:
- Sodium valproate successfully induced autism-like behaviors, including impaired motor coordination, increased anxiety, and social deficits.
- Autistic pups exhibited elevated oxidative stress markers, increased acetylcholinesterase and MAO-A activities, and higher plasma corticosterone levels.
- Palmatine treatment significantly reversed these behavioral, biochemical, and histopathological alterations.
Conclusions:
- Palmatine exhibits significant neuroprotective activity in an animal model of autism spectrum disorder.
- The therapeutic effects of palmatine may be attributed to its ability to reduce brain oxidative stress, inhibit key enzymes, and lower corticosterone levels.
- Palmatine represents a potential therapeutic agent for managing symptoms associated with autism spectrum disorder.
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.
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