Theaflavin Alleviates Memory Deficit and Anxiety-Like Phenotypes in Valproic Acid Murine Model of Autism: Impact on Cholinergic and Oxido-Nitrigic Stress Mechanisms
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Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by deficits in communication and repetitive behaviors. Its etiology is multifactorial, involving genetic, epigenetic, and environmental factors, complicating diagnosis and treatment. This study explores the neuroprotective effects of theaflavin (TF) in a valproic acid (VPA)-induced murine model of autism, focusing on its impact on anxiety, memory, oxidative-nitric stress, and cholinergic pathways. Pregnant Swiss albino mice were injected with VPA (250 mg/kg) on gestational day 13. Male offspring, confirmed to exhibit autistic-like behaviors through tests such as Y-maze, NORT, EPM, LDT, and HBT, were treated with TF (10 or 20 mg/kg) or 1% DMSO (10 mL/kg) for 30 days. Behavioral assessments were repeated post-treatment, and brain samples were analyzed for oxidative stress markers (NO, GSH) and histological damage in the medial prefrontal cortex and hippocampus. VPA-exposed mice showed impaired memory, increased AChE and NO levels, reduced GSH, and neuronal damage. TF significantly improved memory in the Y-maze [F(3, 16) = 9.448; (p = 0.0008)] and NORT [F(3, 16) = 15.12; (p < 0.0001)] but did not significantly affect anxiety-like behaviors in EPM, LDT, or HBT. TF treatment reduced oxidative stress, mitigated neuronal damage, and enhanced cholinergic activity, highlighting its potential as a therapeutic agent for autism.
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