Neuroprotective Efficacy of Fisetin Against VPA-Induced Autistic Neurobehavioral Alterations by Targeting...

Area of Science:

• Neuroscience
• Biochemistry
• Developmental Biology

Background:

• Autism Spectrum Disorder (ASD) is a neurodevelopmental condition linked to oxidative stress and cellular imbalance.
• These cellular changes are associated with behavioral impairments observed in ASD.
• Targeting oxidative stress and redox homeostasis may alleviate autistic symptoms.

Purpose of the Study:

• To investigate the neuroprotective effects of fisetin, a bioflavonoid, in a valproic acid (VPA)-induced rodent model of autism.
• To evaluate fisetin's efficacy when administered during critical developmental windows: gestational and post-weaning periods.
• To determine if fisetin can ameliorate autism-like behaviors and underlying pathophysiology.

Main Methods:

• Autism-like neurobehavior was induced in pregnant rodents using valproic acid (VPA) during neural tube closure.
• Fisetin treatment was administered during the gestational period (GD13-delivery) and post-weaning (PND 23-32).
• Assessed behavioral impairments, oxidative stress markers (ROS, lipid peroxidation), antioxidant levels (glutathione), and enzyme activities (AChE, ATPases) in brain regions.

Main Results:

• VPA exposure led to increased oxidative stress, ROS production, altered enzyme activities, and autistic-like behaviors.
• Both gestational and post-weaning fisetin treatments significantly improved behavioral deficits.
• Fisetin treatment attenuated oxidative stress, restored redox homeostasis, and normalized antioxidant levels and enzyme activities.

Conclusions:

• Fisetin demonstrates significant neuroprotective potential against VPA-induced autism-like symptoms in rodents.
• Its antioxidant properties effectively combat oxidative stress and restore cellular homeostasis.
• Fisetin may serve as a promising therapeutic agent for managing autism-related symptoms.