ArticlePloS one2013
Age-dependent astroglial vulnerability to hypoxia and glutamate: the role for erythropoietin.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
- Article
- Cerebral Hypoxia: Its Role in Age-Related Chronic and Acute Cognitive Dysfunction.Anesthesia and analgesia · 2021Review
- Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer's Mice.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Intranasal injection of recombinant human erythropoietin improves cognitive and visual impairments in chronic cerebral ischemia rats.Biomedical reports · 2020Article
- Alterations in Metabolites Associated with Hypoxemia in Neonates and Infants with Congenital Heart Disease.Congenital heart disease · 2020Article
- Article
- Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide.Redox biology · 2019Article
- Brain Penetrating Bifunctional Erythropoietin-Transferrin Receptor Antibody Fusion Protein for Alzheimer's Disease.Molecular pharmaceutics · 2018Article
- Neuroprotective, Neurogenic, and Amyloid Beta Reducing Effect of a Novel Alpha 2-Adrenoblocker, Mesedin, on Astroglia and Neuronal Progenitors upon Hypoxia and Glutamate Exposure.International journal of molecular sciences · 2017Article
- Neuroprotective effects of erythropoietin on neurodegenerative and ischemic brain diseases: the role of erythropoietin receptor.Neural regeneration research · 2017Review
- Regeneration in the nervous system with erythropoietin.Frontiers in bioscience (Landmark edition) · 2016Review
- Erythropoietin and mTOR: A "One-Two Punch" for Aging-Related Disorders Accompanied by Enhanced Life Expectancy.Current neurovascular research · 2016Review
- Erythropoietin and diabetes mellitus.World journal of diabetes · 2015Review
- Taking aim at Alzheimer's disease through the mammalian target of rapamycin.Annals of medicine · 2014Review
- Progesterone attenuates aquaporin-4 expression in an astrocyte model of ischemia/reperfusion.Neurochemical research · 2014Article
- Interplay between endothelin and erythropoietin in astroglia: the role in protection against hypoxia.International journal of molecular sciences · 2014Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular accumulation of toxic concentrations of glutamate (Glu) is a hallmark of many neurodegenerative diseases, often accompanied by hypoxia and impaired metabolism of this neuromediator. To address the question whether the multifunctional neuroprotective action of erythropoietin (EPO) extends to the regulation of extracellular Glu-level and is age-related, young and culture-aged rat astroglial primary cells (APC) were simultaneously treated with 1mM Glu and/or human recombinant EPO under normoxic and hypoxic conditions (NC and HC). EPO increased the Glu uptake by astrocytes under both NC and especially upon HC in culture-aged APC (by 60%). Moreover, treatment with EPO up-regulated the activity of glutamine synthetase (GS), the expression of glutamate-aspartate transporter (GLAST) and the level of EPO mRNA. EPO alleviated the Glu- and hypoxia-induced LDH release from astrocytes. These protective EPO effects were concentration-dependent and they were strongly intensified with age in culture. More than a 4-fold increase in apoptosis and a 2-fold decrease in GS enzyme activity was observed in APC transfected with EPO receptor (EPOR)-siRNA. Our in vivo data show decreased expression of EPO and a strong increase of EPOR in brain homogenates of APP/PS1 mice and their wild type controls during aging. Comparison of APP/PS1 and age-matched WT control mice revealed a stronger expression of EPOR but a weaker one of EPO in the Alzheimer's disease (AD) model mice. Here we show for the first time the direct correlation between the extent of differentiation (age) of astrocytes and the efficacy of EPO in balancing extracellular glutamate clearance and metabolism in an in-vitro model of hypoxia and Glu-induced astroglial injury. The clinical relevance of EPO and EPOR as markers of brain cells vulnerability during aging and neurodegeneration is evidenced by remarkable changes in their expression levels in a transgenic model of AD and their WT controls.
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