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Neurotoxicology ; 85: 145-159, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34058247

RESUMEN

The amyloid-beta (Aß) 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 Aß oligomers and fibrils. Biocompatible nanoparticles (NPs), e.g., gold and iron oxide NPs, take a unique capacity in redirecting Aß 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 Aß fibrillation and learning and memory processes. In vitro and in vivo findings revealed that Low doses of SPIONs inhibited Aß 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 Aß 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.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Aprendizaje/efectos de los fármacos , Nanopartículas Magnéticas de Óxido de Hierro/administración & dosificación , Trastornos de la Memoria/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Moléculas de Interacción Estromal , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Reacción de Fuga/efectos de los fármacos , Reacción de Fuga/fisiología , Aprendizaje/fisiología , Masculino , Trastornos de la Memoria/metabolismo , Fragmentos de Péptidos/toxicidad , Ratas , Ratas Wistar , Molécula de Interacción Estromal 1/metabolismo , Molécula de Interacción Estromal 2/metabolismo , Moléculas de Interacción Estromal/metabolismo
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