title: Neuroprotective Effect of Nanodiamond in Alzheimer's Disease Rat Model: a Pivotal Role for Modulating NF-κB and STAT3 Signaling.
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.
authors.affiliation: Department of Pharmacy, Faculty of Medicine and Health Sciences, Thamar University, Dhamar, Yemen. shawqialawdi@yahoo.com.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. shawqialawdi@yahoo.com.
authors.forename: Shawqi H
authors.initials: SH
authors.lastname: Alawdi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ezzeldin S
authors.initials: ES
authors.lastname: El-Denshary
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Safar
authors.affiliation: Laboratory of Structure and Activity of Normal and Pathological Biomolecules (SABNP), INSERM U1204, Evry-Val d'Essonne University, 91025, Evry, France.
authors.forename: Housam
authors.initials: H
authors.lastname: Eidi
authors.affiliation: Laboratory of Structure and Activity of Normal and Pathological Biomolecules (SABNP), INSERM U1204, Evry-Val d'Essonne University, 91025, Evry, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: David
authors.affiliation: Department of Food Toxicology and Contaminants, National Research Center, Dokki, Cairo, Egypt. mosaad_abdelwahhab@yahoo.com.
authors.forename: Mosaad A
authors.initials: MA
authors.lastname: Abdel-Wahhab
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D002712:Chlorides / Q000633:toxicity; D004195:Disease Models, Animal; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D058612:Nanodiamonds / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D016328:NF-kappa B; D058612:Nanodiamonds; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D000077410:Aluminum Chloride
keywords: Aluminum; Alzheimer’s disease; Bcl2; NF-κB; Nanodiamond; STAT3