الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disorder impairing memory and cognitive functions that account for more than 80% of dementia cases worldwide. Neuropathologically, amyloid plaques (APs) and neurofibrillary tangles (NFTs) are the two hallmarks of AD. Up till now, there is no effective treatment for AD. Quercetin is a flavonoid with potent antioxidant, anti-inflammatory and radical-scavenger effects but with low bioavailability. However, quercetin nanoparticles (QNPs) have a better bioavailability.
This study was concerned with investigating the possible protective and therapeutic effects of QNPs in aluminum chloride (Alcl3) induced AD and shedding a light on the possible mechanisms of these actions.
Twenty-four male albino rats were used and randomly divided into four groups (6 rats each): control group received QNPs vehicle. AD-group; received Alcl3 (100 mg/kg /day) for 42 days. QNPs were prepared by antisolvent precipitation under sonication and given in a dose of 30 mg/kg /day. The QNPs-prophylactic group received QNPs along with administration of Alcl3, QNPs-treated group received QNPs in the same dose for 42 days after 42 days Alcl3 administration. At the end of the experiment, all animals were sacrificed by decapitation. Brains were harvested and divided into two hemispheres to expose the hippocampi. Right brain hemispheres were rapidly fixed in 10% formalin solution then processed for light microscopic examination; H&E, Bielschowsky’s silver stain, immunocytochemical, and morphometrical studies. Hippocampi from left brain hemispheres were rapidly fixed in 2.5% glutaraldehyde and processed for electron microscopic studies.
The results of the current study revealed that:
• In hematoxylin and eosin stained sections: AD-group showed degenerative changes in pyramidal neurons of CA1 and CA3 regions as well as in granular neurons of DG region of hippocampus. Neuropil vacuolation and capillary congestion also noticed. QNPs in the prophylactic group showed almost prevention of these degenerative changes in CA1, CA2 and DG, while in the treated group it showed some improvement of the previous morphological changes with zonal preference as neurons in CA3 showed the least improvement.
• In Bielschowsky’s silver stained sections: AD model showed APs, NFTs and segmented degenerated axons. QNPs prevent these changes in both prophylactic and treated groups except for few residual NFTs and small sized diffuse plaques in the treated group.
• GFAP immunohistochemical study showed significant increase in GFAP area fraction in AD-group and QNPs-treated groups while QNPs-prophylactic group showed significant decrease compared to AD.
• eNOS immunohistochemical study showed significantly increased area fraction in AD-group with significant decrease in both QNPs-prophylactic and QNPs-treated groups.
• TH immunohistochemical study showed significant decreased area fraction in AD-group. In contrast, QNPs administration in both prophylactic and treated groups showed significant increases compared to AD-group.
• PCNA immunohistochemical study showed significant decrease of granular cells with positive nuclear staining in AD-group. In contrast, QNPs administration in the prophylactic and treated groups showed significant increase in PCNA labelled granular cells in the DG.
• The ultra-structural study: the AD-group showed degenerative changes in hippocampal neurons, myelin sheath and capillaries with blood brain barrier (BBB) disruption. In addition, AD-group showed features of astrocytes and microglial activation. QNPs prevent or improve most of these changes in prophylactic and treated groups respectively, however astrocyte and microglia activation persist in the treated group.
In conclusion, taken together it could be concluded that QNPs could preserve function and structure of neurons, block NFTs and APs formation, restore the hippocampal dopamine levels with subsequent neuronal function improvement, regulate astrocyte and microglial activity, enhance regenerative changes and maintain intact BBB. Using nanoparticles of quercetin might provide a new line for prevention or delaying the AD onset in susceptible people. In addition, it could minimize the degenerative changes of AD affected hippocampus (not completely abolished).