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Resveratrol-Selenium Nanoparticles Alleviate Neuroinflammation and Neurotoxicity in a Rat Model of Alzheimer’s Disease by Regulating Sirt1/miRNA-134/GSK3β Expression

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Abstract

Alzheimer’s disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid β (Aβ). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3β)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1β (IL-1β) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer’s disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways.

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Data Availability

All the data are available in the current study.

Abbreviations

Al:

Aluminum

AD:

Alzheimer’s disease

Aβ:

Amyloid β

MSCs:

mesenchymal stem cells

SIRT:

sirtuin

AlCl3 :

aluminum chloride

MDA:

malondialdehyde

CAT:

catalase

H2O2 :

hydrogen peroxide

GSH:

glutathione

IL-1β:

interleukin-1β

ANOVA:

one-way analysis of variance

LSD:

least significant difference

SE:

standard error

STAT3:

signal transducer and activator of transcription

PI3K:

phosphatidylinositol 3 kinase

GSK3β:

glycogen synthase kinase 3 beta

MiR-134:

microRNA- 134

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Veterinary Medicine, Benha University, Benha, Egypt

    Omayma A. R. Abozaid, Mohsen W. Sallam & Samy Aziza

  2. National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt

    Sawsan El-Sonbaty

  3. Anatomy and Embryology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Basma Emad

  4. Radiation Biology, National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo, 11787, Egypt

    Esraa S. A. Ahmed

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  1. Omayma A. R. Abozaid
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  3. Sawsan El-Sonbaty
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  4. Samy Aziza
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Correspondence to Esraa S. A. Ahmed.

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The experimental protocol was carried out according to the Guide for the Care and Use of Laboratory Animals (NIH no. 85–23, 1985).

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Abozaid, O.A.R., Sallam, M.W., El-Sonbaty, S. et al. Resveratrol-Selenium Nanoparticles Alleviate Neuroinflammation and Neurotoxicity in a Rat Model of Alzheimer’s Disease by Regulating Sirt1/miRNA-134/GSK3β Expression. Biol Trace Elem Res 200, 5104–5114 (2022). https://doi.org/10.1007/s12011-021-03073-7

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