The Neuroprotective Effect of Ginkgo Biloba Extract on Valproic Acid Induced Autistic Features in Mice

Abstract

Introduction: Autism Spectrum Disorders (ASD) are among the severe developmental disorders, but have no specific treatments available. Ginkgo biloba (GK) has been reported to affect the neurotransmitter system and have anti-oxidant and anti-inflammatory properties that could impact the pathogenesis of valproic acid-induced autistic features. Aim: To identify the neuromodulatory effects of Ginkgo biloba extract on ASD induced by valproic acid in mice. Materials and Methods: A total of 24 male Wistar albino mice, 14-day-old, were used and divided into four groups (6 mice/group): Control, Ginkgo biloba extract-treated group {received GK at a dose 100 mg/kg via intraperitoneal injection once daily from Postnatal Day (PND) 13 to PND 40}, Valproic acid-treated group (VPA) (received Sodium Valproate at a dose 400 mg/kg via subcutaneous injection once on PND14), and Valproic acid + Ginkgo biloba extract-treated group (received VPA on PND14 and GK from PND 13 to PND 40). Neuro-behaviour tests (Open field, Social approach (three-chamber) test and T-maze spontaneous alternation) of mice were assessed. Biochemical tests (brain tissue malondialdehyde (MDA), Glutathione (GSH), Interleukin-6 (IL-6), Transforming Growth Factor-Beta (TGF-β1) and serum interleukin-17 (IL-17) were done. Also, histopathological, immunohistochemical and morphometric studies for the cerebellum were done. Analysis of Variances (ANOVA) was used for statistical analysis of the different groups followed by a post-hoc Tukey test. Results: VPA showed significant neuro-behavioural changes with a significant increase of (MDA, IL-6 and IL-17) and a significant decrease in (GSH and TGF-β1). Histopathological results revealed widespread neuronal affection, specifically of the Purkinje Cells (PCs) layer with a significant decrease in the expression of Myelin Basic Protein (MBP) and Serotonin. Ginkgo biloba ameliorated significantly VPA-induced autistic changes. Conclusion: Ginkgo biloba extract can ameliorate the autistic changes in mice through its anti-inflammatory and anti-oxidant activities in addition to its ability to modulate serotonin and MBP expression. It can be concluded that GK can be used as a potential disease-modifying treatment for Autism.