Abscisic Acid Enhances Hippocampal Neuroplasticity and Rescues Learning and Memory Deficits in a Valproate-Induced Rat Model of Autism

OBJECTIVES: This study investigated the possible protective effects of abscisic acid (ABA), a naturally occurring phytohormone with incipient neuromodulatory properties, to alleviate cognitive and neurological alterations in a valproate (VPA)-induced rat model of autism. METHODS: ABA was injected intra-CA1 hippocampal (0.5, 1, 1.5 μg/rat) in both VPA-exposed and control rats. Spatial learning and memory retention was validated by Morris water maze (MWM). Additionally, hippocampal levels of oxidative stress biomarkers-hydrogen peroxide (H₂O₂) and malondialdehyde (MDA)-were quantified. The expression of key neuroplasticity-related genes (BDNF, TrkB, PI3K and AKT) was also evaluated via real-time PCR. RESULTS: VPA-exposed rats exhibited significant deficits in learning and memory, alongside elevated hippocampal oxidative stress and downregulation of BDNF/TrkB and PI3K/AKT signalling. ABA treatment dose-dependently reversed learning and memory impairments. Moreover, ABA (1.5 μg/rat) significantly reduced H₂O₂ and MDA levels and restored the gene expression of BDNF, TrkB, PI3K and AKT in the hippocampus, indicating coordinated enhancement of antioxidant defences and neurotrophic transcriptional activity. However, ABA's efficiency in improving these responses was completely blocked by nifedipine, a calcium channel blocker, and chelerythrine, a PKC inhibitor. DISCUSSION: Overall, our results highlight the promising potential of ABA as a treatment for ASD while emphasising the necessity for more research to entirely elucidate its underlying mechanisms.