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.