Abstract
Background: In recent years, scientists have discovered that nanoparticles can effectively aid in the treatment of neurodegenerative diseases. This study aimed to explore the effects of ascorbic acid (AA) encapsulated in chitosan nanoparticles on neuroprotection in a rat model of Alzheimer's disease. We employed biochemical, molecular, histological, and behavioral methods to achieve this purpose. Methods: Alzheimer's disease was induced in the rats through an intracerebroventricular injection of amyloid beta (Aβ)1-42. After the induction, the animals received either AA or nano-AA at a dosage of 100 mg/kg orally for one month. Results: Both treatments effectively prevented the decrease in superoxide dismutase activity and the increase in malondialdehyde levels in the hippocampus of the Aβ-injected rats. In addition, both AA and nano-AA inhibited the elevation of monocyte chemoattractant protein-1 and beta-secretase-1 expression. They also reduced amyloid plaque deposition and neuronal death in the hippocampal cornus ammonis 1 area. Moreover, the treatments led to improvements in spatial learning and memory. AA and nano-AA prevented the rise in indoleamine 2,3-dioxygenase-1 expression in the hippocampus, reduced kynurenine levels, and increased serotonin levels. Notably, nano-AA demonstrated greater effectiveness than AA across all observed factors, except for memory improvement. Conclusion: In conclusion, encapsulating AA in chitosan nanoparticles enhances the antioxidant's ability to reduce oxidative stress and inflammation, improve histological damage, and regulate serotonin metabolism in the hippocampus of rats modeled for Alzheimer's disease.