NDLI: Age-Dependent Astroglial Vulnerability to Hypoxia and Glutamate: The Role for Erythropoietin

Content Provider	PubMed Central
Author	Ali, Lourhmati Buniatian, Gayane H. Paul, Christina Stephan, Verleysdonk Buecheler, Reinhild Marine, Buadze Proksch, Barbara Schwab, Matthias Gleiter, Christoph H. Danielyan, Lusine
Editor	François, Blachier
Copyright Year	2013
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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0077182
Starting Page	77182
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Ceftriaxone Preserves Glutamate Transporters and Prevents Intermittent Hypoxia-Induced Vulnerability to Brain Excitotoxic Injury

A Role for Glutamate Transporters in the Regulation of Insulin Secretion

The Role of Seagrass Traits in Mediating Zostera noltei Vulnerability to Mesograzers

Mimicking Hypoxia to Treat Anemia: HIF-Stabilizer BAY 85-3934 (Molidustat) Stimulates Erythropoietin Production without Hypertensive Effects

Acute Vhl Gene Inactivation Induces Cardiac HIF-Dependent Erythropoietin Gene Expression

Ammonia Affects Astroglial Proliferation in Culture

Using Age-Based Life History Data to Investigate the Life Cycle and Vulnerability of Octopus cyanea

“Super p53” Mice Display Retinal Astroglial Changes

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

Age-Dependent Astroglial Vulnerability to Hypoxia and Glutamate: The Role for Erythropoietin

Similar Documents

Ceftriaxone Preserves Glutamate Transporters and Prevents Intermittent Hypoxia-Induced Vulnerability to Brain Excitotoxic Injury

A Role for Glutamate Transporters in the Regulation of Insulin Secretion

The Role of Seagrass Traits in Mediating Zostera noltei Vulnerability to Mesograzers

Mimicking Hypoxia to Treat Anemia: HIF-Stabilizer BAY 85-3934 (Molidustat) Stimulates Erythropoietin Production without Hypertensive Effects

Acute Vhl Gene Inactivation Induces Cardiac HIF-Dependent Erythropoietin Gene Expression

Ammonia Affects Astroglial Proliferation in Culture

Using Age-Based Life History Data to Investigate the Life Cycle and Vulnerability of Octopus cyanea

“Super p53” Mice Display Retinal Astroglial Changes

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

Age-Dependent Astroglial Vulnerability to Hypoxia and Glutamate: The Role for Erythropoietin