title: Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK-PKC-CBP signaling cascade.
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.
authors.affiliation: Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, Timarpur, Delhi, India.
authors.forename: Aditya
authors.initials: A
authors.lastname: Arya
authors.affiliation: Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, Timarpur, Delhi, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Gangwar
authors.affiliation: Functional Materials Division, Solid State Physics Laboratory, Defense Research and Development Organization, Timarpur, Delhi, India.
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Biological Science and Bioengineering, Indian Institute of Technology, Kanpur, India; Department of Chemistry, Indian Institute of Engineering Science and Technology, Howrah, India.
authors.forename: Manas
authors.initials: M
authors.lastname: Roy
authors.affiliation: Biological Science and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors.forename: Mainak
authors.initials: M
authors.lastname: Das
authors.affiliation: Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, Timarpur, Delhi, India.
authors.forename: Niroj Kumar
authors.initials: NK
authors.lastname: Sethy
authors.affiliation: Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, Timarpur, Delhi, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Bhargava
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002563:Cerium / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008565:Membrane Proteins; C408142:Pag1 protein, rat; D010750:Phosphoproteins; D002563:Cerium; C030583:ceric oxide; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases
keywords: cerium oxide nanoparticles; hypoxia; memory; neuroprotection; oxidative stress