الفهرس 
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Abstract
The present study aimed to investigate the potential neuroprotective role of zinc oxide nanoparticles (ZnONPs) against aluminum chloride (AlCl3)-induced Alzheimer’s disease (AD)-like symptoms in rats. Thirty two male albino rats were allocated into four equal groups as follow: Control, ZnONPs intraperitoneally (i.p) injected group (4 mg/kg b.wt.), AlCl3 orally administered group (100 mg/kg b.wt.) and ZnONPs+AlCl3 treated group. The treatment were daily extended for 42 consecutive days. AlCl3-treated rats showed a disturbance in the oxidative status in the cerebral cortex and hippocampus, as evidenced by the elevated malondialdehyde (MDA), nitric oxide (NO) levels and superoxide dismutase (SOD) activity accompanied by a decrease in glutathione (GSH) content and catalase (CAT) activity. Additionally, AlCl3 triggered a state of neuroinflammation in the tested brain regions through enhancing the production of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Moreover, apoptotic cascade was recorded following AlCl3 exposure as indicated by increased caspase-3 activity and decreased B-cell lymphoma 2 (Bcl-2) levels. Furthermore, oral administration of AlCl3 impaired the cholinergic activity in the examined brain tissues as evidenced by the over activation of acetylcholinesterase (AChE). A disturbance in the monoaminergic transmission was also recorded following AlCl3 administration as confirmed by the decreased norepinephrine (NE), dopamine (DA) and 5-Hydroxytryptamine (5-HT, serotonin) contents. The exposure to AlCl3 increased the levels of excitatory amino acids (glutamic and aspartic acids), while decreased the levels of the inhibitory amino acids (γ-aminobutyric acid (GABA) and glycine) in the cerebral cortex and hippocampus. On the other hand, the daily i.p injected rats with ZnONPs before AlCl3 was found to inhibit significantly the molecular, biochemical, neurochemical and histopathological alterations in response to AlCl3 exposure. These results suggest that ZnONPs could be used as alternative therapy to minimize the neurological deficits associated with the progression of AD through its antioxidant, anti-inflammatory, anti-apoptotic and neuromodulatory activities.