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Molecular Neurobiology

, Volume 54, Issue 3, pp 1906–1918 | Cite as

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

  • Shawqi H. AlawdiEmail author
  • Ezzeldin S. El-Denshary
  • Marwa M. Safar
  • Housam Eidi
  • Marie-Odile David
  • Mosaad A. Abdel-WahhabEmail author
Article

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

Nanodiamond Alzheimer’s disease STAT3 Bcl2 NF-κB Aluminum 

Abbreviations

AD

Alzheimer’s disease

Aβ42

Amyloid beta 1–42

AlCl3

Aluminum chloride

BACE1

Beta site amyloid precursor protein cleaving enzyme-1

BDNF

Brain-derived neurotrophic factor

Bcl2

B cell leukemia/lymphoma 2

Bax

Bcl-2-associated X protein

Bak

Bcl-2-antagonist/killer-1

Casp-3

Caspase-3

GSK-3

Glycogen synthase kinase-3

iNOS

Inducible nitric oxide synthase

IL-6

Interleukin-6

MEM

Memantine

MWM

Morris water maze

ND

Nanodiamond

NF-κB

Nuclear factor kappa-B

NMDA

N-methyl-D-aspartate

p-STAT3

Phosphorylated signal transducer and activator of transcription-3

p-tau

Phosphorylated tau protein

TFAM

Mitochondrial transcription factor A

TNF-α

Tumor necrosis factor alpha

TrKB

Tyrosine receptor kinase B

Notes

Acknowledgments

The authors are grateful to Dr. Adel Kholoussy (Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt) for his assistance in histopathology and Dr. Waleed Ali (Department of Biochemistry, Faculty of Medicine, Cairo University, Egypt) for his assistance in biochemical analysis. Author Shawqi Alawdi would also like to thank Thamar University, Yemen, for supporting his PhD study.

Compliance with Ethical Standards

All animal procedures were performed in accordance with the ethical procedures and policies approved by the Research Ethics Committee for Experimental and Clinical Studies of Faculty of Pharmacy, Cairo University, Egypt, and comply with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication no. 85–23, revised 1996). All efforts were exerted to minimize animal suffering.

Conflict of Interest

The authors declare that there are no conflicts of interest in this work.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shawqi H. Alawdi
    • 1
    • 2
    Email author
  • Ezzeldin S. El-Denshary
    • 2
  • Marwa M. Safar
    • 2
  • Housam Eidi
    • 3
  • Marie-Odile David
    • 3
  • Mosaad A. Abdel-Wahhab
    • 4
    Email author
  1. 1.Department of Pharmacy, Faculty of Medicine and Health SciencesThamar UniversityDhamarYemen
  2. 2.Department of Pharmacology and Toxicology, Faculty of PharmacyCairo UniversityCairoEgypt
  3. 3.Laboratory of Structure and Activity of Normal and Pathological Biomolecules (SABNP), INSERM U1204Evry-Val d’Essonne UniversityEvryFrance
  4. 4.Department of Food Toxicology and ContaminantsNational Research CenterCairoEgypt

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