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Mol Neurobiol. 2017 Apr;54(3):1906-1918. doi: 10.1007/s12035-016-9762-0. Epub 2016 Feb 20.

Neuroprotective Effect of Nanodiamond in Alzheimer's Disease Rat Model: a Pivotal Role for Modulating NF-κB and STAT3 Signaling.

Author information

1
Department of Pharmacy, Faculty of Medicine and Health Sciences, Thamar University, Dhamar, Yemen. shawqialawdi@yahoo.com.
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. shawqialawdi@yahoo.com.
3
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
4
Laboratory of Structure and Activity of Normal and Pathological Biomolecules (SABNP), INSERM U1204, Evry-Val d'Essonne University, 91025, Evry, France.
5
Department of Food Toxicology and Contaminants, National Research Center, Dokki, Cairo, Egypt. mosaad_abdelwahhab@yahoo.com.

Abstract

Current therapeutic approaches of Alzheimer's disease (AD) are symptomatic and of modest efficacy, and there is no available effective cure or prevention of AD; hence, the need arise to search for neuroprotective agents to combat AD. The current study aimed at investigating the neuroprotective effect of nanodiamond (ND), adamantine-based nanoparticles, in aluminum-induced cognitive impairment in rats, an experimental model of AD. AD was induced by aluminum chloride (17 mg/kg, p.o. for 6 weeks) and confirmed by Morris water maze and Y-maze behavioral tests. Biochemical and histological analyses of the hippocampus were also performed. Aluminum-treated rats showed behavioral, biochemical, and histological changes similar to those associated with AD. ND improved learning and memory and reversed histological alterations. At the molecular levels, ND mitigated the increase of hippocampal beta-amyloid (Aβ42) and beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) together with down-regulation of phosphorylated tau protein. It also modulated the excitatory glutamate neurotransmitter level. Furthermore, ND boosted the brain-derived neurotrophic factor (BDNF) and mitochondrial transcription factor-A (TFAM), suppressed the proinflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and curbed oxidative stress by hampering of inducible nitric oxide synthase (iNOS). Moreover, ND augmented the hippocampal levels of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and B cell leukemia/lymphoma-2 (Bcl-2) anti-apoptotic protein while diminished nuclear factor-kappaB (NF-κB) and caspase-3 (casp-3) expression. These findings indicate the protective effect of ND against memory deficits and AD-like pathological aberrations probably via modulating NF-kB and STAT3 signaling, effects mediated likely by modulating N-methyl-D-aspartate (NMDA) receptors.

KEYWORDS:

Aluminum; Alzheimer’s disease; Bcl2; NF-κB; Nanodiamond; STAT3

PMID:
26897372
DOI:
10.1007/s12035-016-9762-0
[Indexed for MEDLINE]

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