The effect of yttrium oxide nanoparticles on memory, inflammatory responses and mitochondrial biogenesis in cholestatic male Wistar rats

Background and Objectives: Cholestasis can lead to oxidative stress, inflammation, apoptosis, mitochondrial dysfunction and ultimately causes cognitive damage, such as memory malfunctions. Considering their anti-inflammatory and protective effects, nanoparticles may be effective for the treatment of neurological disorders or for transferring medications through the blood-brain barrier. This study investigated the protective effect of yttrium oxide nanoparticles (Y2O3NPs) on cognitive disorders, inflammatory response and mitochondrial biogenesis caused by cholestasis in rat hippocampus. Methods: Male Wistar rats were randomly divided into seven groups: control, sham, vehicle, cholestasis, and three groups of cholestatic rats, which received doses of 0.1, 0.3, and 0.5 mg/kg Y2O3NPs, respectively for 21 days. The Morris water maze, passive avoidance, and elevated plus maze tests were used to assess the learning and memory of the rats. The expression of genes involved in mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM) and pro-inflammatory genes (TNF-α, IL-6, and IL-1β) were evaluated by real-time PCR technique. Results: Cholestasis led to learning and memory dysfunctions, decreased the expression of genes involved in mitochondrial biogenesis, and increased the expression of genes involved in neuroinflammation. Intraperitoneal injection (IP) of Y2O3NPs, especially at a dose of 0.5 mg/kg, enhanced the recognition and recall memory, increased the expression of factors involved in mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM), and decreased neuroinflammation (TNF-α, IL-6, and IL-1β). Conclusion: This study demonstrated that Y2O3NPs reduced memory disorders caused by cholestasis. This nanoparticle increased the expression of factors involved in mitochondrial biogenesis, reduced the inflammatory responses in the hippocampus of cholestasis animals, and possibly alleviated cognitive disorders through this mechanism.