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 (Aβ) 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.

FGF21 Attenuates High-Fat Diet-Induced Cognitive Impairment via Metabolic Regulation and Anti-inflammation of Obese Mice

“…In the Y-maze test, mice were transferred from the home cage to the center of the maze and were allowed to explore the three arms freely for 5 min. Each alternation trial was captured by a digital video and the video clips were analyzed offline, in a blind manner as previously described [42]. An entry was recorded when all four limbs were within an arm.…”

Advance of sporadic Alzheimer's disease animal models

“…Adult male Wistar rats administrated orally with AlCl 3 (17 mg·kg −1 ·d −1 ) for 6 weeks developed AD‐like pathologies. Compared with the control group, the levels of BACE1, Aβ 1‐42 , phosphorylated Tau protein, tumour necrosis factor α, and IL‐6 in rat hippocampus and cortex of the model group were all increased . However, the barrier function of the endothelium of cerebral cortex blood microvessels were not noticeably affected in ICR mice administrated orally with AlCl 3 10 mg·kg −1 ·d −1 for 100 days .…”

“…24,143,144 Redox hippocampus and cortex of the model group were all increased. 150 However, the barrier function of the endothelium of cerebral cortex blood microvessels were not noticeably affected in ICR mice administrated orally with AlCl 3 10 mg·kg −1 ·d −1 for 100 days. 151 When Male Wistar rats aged 18 to 20 months were intraperitoneally injected with AlCl 3 (4.2 mg·kg −1 d −1 ) for 60 days, the activity of acetylcholinesterase and MDA in the blood and brain increased, the level of SOD decreased, and the reactive glial cells in the hippocampus and cortex increased.…”

“…56,80,122 Moreover, AD is a progressive neural disorder, ZHANG ET AL. [149][150][151][152] Abbreviations: AAV1, adeno-associated virus serotype 1; AChE, acetylcholinesterase; AD, Alzheimer' disease; Aβ, | 449 therefore, a chronic animal model might be better than an acute one. The acrolein-induced model can simulate the toxic effects of daily exposure to acrolein and could be closer to the development of AD.…”

Engineered BDNF producing cells as a potential treatment for neurologic disease

“…[88] Nanoparticle-mediated therapy elevated BDNF in the hippocampus mitigated levels of Aβ and tau proteins while augmenting neuronal cell survival in AD transgenic rats. [89] Overexpression of BDNF using mesenchymal stem cells (MSCs) in HD mouse models have shown amelioration of behavioral deficits in HD mouse models,[90] increased striatal volume and neurogenesis. [12]…”