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.

Nanocerium oxide increases the survival of adult rod and cone photoreceptor in culture by abrogating hydrogen peroxide-induced oxidative stress

“…The earlier studies which were performed on understanding the antioxidant role of ceria were carried out in mammalian systems. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] In the present study, similar antioxidant activity was observed in adult fish PR neurons. This offers a new experimental animal tool to explore the long-term genetic effects of nanoparticle treatment.…”

“…Recent in vivo studies has shown that in the brain, it promotes neurogenesis and abrogate hypoxia-induced memory impairment and protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation. 41,44 V. CONCLUSION Here, it has been shown that fortification of the adult photoreceptor culture with a single dose of nanoceria at the time of plating the cells significantly increases the survival of both rod and cone cells. Thus, this system could find applications in understanding the basic photoreceptor physiology as well as in high throughput drug screening against all kinds of age related retinal blindness.…”

“…(2) exhibiting reactive oxygen species (ROS)/reactive nitrogen species scavenging activity. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] The next question is how ceria exhibit antioxidative activity in aqueous solution. A part of the answer lies in the surface chemical features of nanoceria and the subsequent interaction in an aqueous medium.…”

“…It mimics the activity of classical antioxidant enzymes like catalase and SOD. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] As discussed in the earlier paragraphs that in terms of testing the possibility of enhancing the life span of adult PR cells in the culture (ex vivo) by treating them with nanoceria was not explored. Since the age related retinal blindness like inherited retinal degeneration, macular degeneration, diabetic retinopathy, and retinal detachment occurs due to the aging of PR neurons, so it is all the more imperative to target this unanswered question: "whether nanoceria could support the long-term survival of adult photoreceptor cells in the culture?"…”

Synthesis of Cuboctahedral CeO2 Nanoclusters and Their Assembly into Cuboid Nanoparticles by Oriented Attachment

“…In the last decade, significant progress has been made in the synthesis and assembly of nanocrystals, and has allowed the control of their compositions, sizes, shapes,a nd functionalities. [1][2][3][4] More recently,e fforts have focused on the use of nonclassical nucleation and growth approaches, which allow the development of nanocrystals and nanoparticles with high complexity in terms of shape,composition, and enhanced functionality. [5][6][7] An important mechanism related to the non-classical approachi st he aggregation of nanoclustersa nd nanoparticles.…”