Linalool vs linalool-loaded chitosan nanoparticles in an Aβ-induced rat model of Alzheimer’s disease: A molecular, biochemical, histological, and behavioral study

Objective(s): Recent studies have increasingly focused on applying nanotechnology to treat neurodegenerative diseases. In this study, we compared the effects of the monoterpene linalool and linalool-loaded chitosan nanoparticles on key pathological features of Alzheimer’s disease (AD), including oxidative stress, neuroinflammation, neuronal death, amyloid plaque deposition, alterations in tryptophan metabolism, and memory deficit in a rat model of AD. Materials and Methods: An intracerebroventricular injection of Aβ۴۲ (۱۰ µg) was used to induce the AD model. Linalool (۲۵ mg/kg) and nano-linalool (۲۵ mg/kg) were administered orally once daily for ۳۰ consecutive days. Results: Both linalool and nano-linalool significantly reduced malondialdehyde levels and enhanced superoxide dismutase activity in the hippocampus. They also decreased the mRNA levels of monocyte chemoattractant protein-۱, inhibited the up-regulation of beta-secretase, reduced amyloid plaque deposition, and attenuated pyramidal neuron death in the CA۱ region. Additionally, treatment with both compounds down-regulated indoleamine ۲,۳-dioxygenase, lowered kynurenine levels, and increased serotonin concentrations in the hippocampus. Although both treatments improved learning and spatial memory in Aβ-injected rats, nano-linalool’s effectiveness was more significant than that of linalool in modulating the molecular, biochemical, and histological parameters.Conclusion: Encapsulating linalool in chitosan nanoparticles enhances its effectiveness in improving molecular, biochemical, and histological changes in the hippocampus of rat models of AD.

کلیدواژه ها:

Alzheimer’s disease ، Amyloid precursor protein - secretases ، Hippocampus ، Kynurenine ، Linalool-loaded chitosan - nanoparticle ، Oxidative stress ، Spatial Memory