PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) ameliorate learning and memory deficit in a rat model of Alzheimer's disease: Potential participation of STIMs

The amyloid-beta (A beta) fibrillation process seems to execute a principal role in the neuropathology of Alzheimer's disease (AD). Accordingly, novel therapeutic plans have concentrated on the inhibition or degradation of A beta oligomers and fibrils. Biocompatible nanoparticles (NPs), e.g., gold and iron oxide NPs, take a unique capacity in redirecting A beta fibrillation kinetics; nevertheless, their impacts on AD-related memory impairment have not been adequately evaluated in vivo. Here, we examined the effect of commercial PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) on the learning and memory of an AD-animal model. The outcomes demonstrated the dose-dependent effect of SPIONs on A beta fibrillation and learning and memory processes. In vitro and in vivo findings revealed that Low doses of SPIONs inhibited A beta aggregation and ameliorated learning and memory deficit in the AD model, respectively. Enhanced level of hippocampal proteins, including brain-derived neurotrophic factor, BDNF, phosphorylated-cAMP response element-binding protein, p-CREB, and stromal interaction molecules, e.g., STIM1 and STIM2, were also observed. However, at high doses, SPIONs did not improve the detrimental impacts of A beta fibrillation on spatial memory and hippocampal proteins expression. Overall, we revealed the potential capacity of SPIONs on retrieval of behavioral and molecular manifestations of AD in vivo, which needs further investigations to determine the mechanistic effect of SPIONs in the AD conundrum.

Automated summary

Low doses of SPIONs inhibit Aβ aggregation and ameliorate learning and memory deficits in the AD model, while also increasing hippocampal protein levels. However, at high doses, SPIONs do not improve the detrimental effects of Aβ aggregation on spatial memory and hippocampal protein expression.