Introduction: The potential benefits of natural ingredients in the alleviation of neurodegenerative disorders are of great interest. Alpha-pinene (APN) is an essential oil belonging to monoterpenes with multiple beneficial effects. In this study, the possible improving effects of alpha-pinene on memory impairment induced by kainic acid and the underlying molecular mechanisms were examined. Methods: Memory impairment was induced by i.c.v. injection of kainic acid (KA) in male Wistar rats. Alpha-pinene (50 mg/kg/day, i.p.) was injected for 21 days, including 14 days before the KA injection and seven days afterward. Spatial working memory and inhibitory avoidance (IA) memory performance were assessed five and even days following KA injection, respectively. The hippocampal protein levels of brain-derived neurotrophic factor (BDNF), tropomyosin-like receptor kinase B (TrkB), cAMP response element binding protein (CREB), and neuronal loss in the CA1 region were also examined. Results: Results revealed that the i.c.v. injection of KA triggered memory impairment, which was notably diminished by alpha-pinene pre-and post-treatment. Histopathological evaluation revealed that alpha-pinene significantly moderated the attenuation in CA1 alive neurons induced by KA injection. Western blotting analysis confirmed that alpha-pinene pre-and post-treatment significantly reversed the KA-induced decreases in the hippocampal levels of BDNF, TrkB, phosphorylated TrkB, CREB, and phosphorylated CREB. Discussion: These findings suggest that alpha-pinene pre-and post-treatment moderate memory impairment induced by KA by restoring the BDNF/TrkB/CREB signaling pathway in the rat hippocampus.
