Yttrium oxide nanoparticles alleviate cognitive deficits, neuroinflammation, and mitochondrial biogenesis impairment induced by streptozotocin.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive decline. Yttrium oxide nanoparticles (Y 2 O 3 NPs) have recently attracted much attention for their potential anti-inflammatory and antioxidant properties. However, the effects of Y 2 O 3 NPs in animal models of AD are less studied. This study aimed to investigate the potential therapeutic effects of Y 2 O 3 NPs in streptozotocin (STZ)-treated rats, a reliable animal model of AD, with special emphasis on cognitive function, neuroinflammation, and mitochondrial biogenesis in the hippocampus. Male Wistar rats were stereotaxically injected with STZ (3 mg/kg, 3 µl/ventricle). Three weeks after STZ injection, cognitive function was assessed using the Morris water maze, elevated plus maze, and passive avoidance tasks. Intraperitoneal treatment with Y 2 O 3 NPs (0.1, 0.3, or 0.5 mg/kg) was started 24 h after the STZ injection and continued for 21 days. The mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and components involved in mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM) were measured in the hippocampus. The results indicated that STZ induced cognitive impairment and led to neuroinflammation and mitochondrial biogenesis impairment in the hippocampus of rats. Interestingly, treatment with Y 2 O 3 NPs effectively reduced STZ-induced cognitive deficits in a dose-dependent manner, possibly by attenuating neuroinflammation and mitochondrial biogenesis impairment. These findings suggest that Y 2 O 3 NPs can be considered as a promising therapeutic agent for treating or ameliorating the neuropathological effects associated with AD.