http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818056/
Abstract
Structural
and functional integrity of the brain is adversely affected by reduced
oxygen saturation, especially during chronic hypoxia exposure and often
encountered by altitude travelers or dwellers. Hypoxia-induced
generation of reactive nitrogen and oxygen species reportedly affects
the cortex and hippocampus regions of the brain, promoting memory
impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs),
also known as nanoceria, switch between +3 and +4 oxidation states and
reportedly scavenge superoxide anions, hydrogen peroxide, and
peroxynitrite in vivo. In the present study, we evaluated the
neuroprotective as well as the cognition-enhancing activities of
nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3
nm nanoceria (PEG-CNPs), we have demonstrated efficient localization of
PEG-CNPs in rodent brain. This resulted in significant reduction of
oxidative stress and associated damage during hypoxia exposure. Morris
water maze-based memory function tests revealed that PEG-CNPs
ameliorated hypoxia-induced memory impairment. Using microscopic, flow
cytometric, and histological studies, we also provide evidences that
PEG-CNPs augmented hippocampus neuronal survival and promoted
neurogenesis. Molecular studies revealed that PEG-CNPs promoted
neurogenesis through the 5′-adenine monophosphate-activated protein
kinase–protein kinase C–cyclic adenosine monophosphate response
element-binding protein binding (AMPK-PKC-CBP) protein pathway. Our
present study results suggest that nanoceria can be translated as
promising therapeutic molecules for neurodegenerative diseases.
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