Synaptic NMDA receptors mediate hypoxic excitotoxic death.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Christine M WrogeSteven Mennerick

Abstract

Excessive NMDA receptor activation and excitotoxicity underlies pathology in many neuropsychiatric and neurological disorders, including hypoxia/ischemia. Thus, the development of effective therapeutics for these disorders demands a complete understanding of NMDA receptor (NMDAR) activation during excitotoxic insults. The extrasynaptic NMDAR hypothesis posits that synaptic NMDARs are neurotrophic/neuroprotective and extrasynaptic NMDARs are neurotoxic. The extrasynaptic hypothesis is built in part on observed selectivity for extrasynaptic receptors of a neuroprotective use-dependent NMDAR channel blocker, memantine. In rat hippocampal neurons, we found that a neuroprotective concentration of memantine shows little selectivity for extrasynaptic NMDARs when all receptors are tonically activated by exogenous glutamate. This led us to test the extrasynaptic NMDAR hypothesis using metabolic challenge, where the source of excitotoxic glutamate buildup may be largely synaptic. Three independent approaches suggest strongly that synaptic receptors participate prominently in hypoxic excitotoxicity. First, block of glutamate transporters with a nonsubstrate antagonist exacerbated rather than prevented damage, consistent with a primarily s...Continue Reading

References

Jan 1, 1990·Annual Review of Neuroscience·D W Choi, S M Rothman
Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J M BekkersC F Stevens
Apr 29, 1983·Science·S M Rothman
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·D JabaudonU Gerber
May 23, 2001·Progress in Neurobiology·N C Danbolt
Sep 21, 2001·Journal of Neuroscience Methods·S M Potter, T B DeMarse
Nov 26, 2002·Biochimica Et Biophysica Acta·Giles E Hardingham, Hilmar Bading
Dec 22, 2005·Current Opinion in Pharmacology·Jon W Johnson, Shawn E Kotermanski
Apr 28, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Francesc X SorianoGiles E Hardingham
Jul 5, 2006·The European Journal of Neuroscience·Christiane VolbrachtMarcel Leist
Aug 4, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jun YaoGong Chen
Nov 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Laurent GrocDaniel Choquet
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yitao LiuYu Tian Wang
Aug 25, 2007·The Journal of Physiology·Alexander Z Harris, Diana L Pettit
Sep 21, 2007·Nature Reviews. Neuroscience·Stuart A Lipton
Mar 18, 2008·Nature Neuroscience·Sofia PapadiaGiles E Hardingham
Aug 20, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·F LéveilléA Buisson
Mar 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shawn E Kotermanski, Jon W Johnson
Jun 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ruslan I StanikaS Brian Andrews
Aug 19, 2009·The Journal of Physiology·Shawn E KotermanskiJon W Johnson
Feb 26, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Steven MennerickCharles F Zorumski
Aug 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Peng XiaStuart A Lipton
Sep 16, 2010·Nature Reviews. Neuroscience·Giles E Hardingham, Hilmar Bading
Nov 26, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karim BordjiAlain Buisson
May 24, 2011·Molecular and Cellular Neurosciences·Clare M Gladding, Lynn A Raymond
May 25, 2011·Neurobiology of Disease·Joshua HoginsSteven Mennerick
Oct 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David T Stark, Nicolas G Bazan
Jan 13, 2012·Journal of Neurophysiology·Nadezhda V Povysheva, Jon W Johnson

❮ Previous
Next ❯

Citations

Jan 25, 2014·Lancet Neurology·Henrik HagbergClaire Thornton
Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Maria TalantovaStuart A Lipton
Nov 13, 2012·Molecular Pharmacology·Andrew J LinsenbardtSteven Mennerick
Jan 23, 2013·International Journal of Molecular Medicine·Nada SamariMohammed Abderrafi Benotmane
Jun 5, 2013·Archives of Pharmacal Research·Jihyun NohJun-Mo Chung
Jul 19, 2014·The Journal of Clinical Investigation·Federico N SoriaMaría Domercq
Sep 17, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Thomas Papouin, Stéphane H R Oliet
Dec 29, 2012·Brain Research Bulletin·Dan-dan LiuSheng-tian Li
Apr 22, 2015·Computational and Structural Biotechnology Journal·Denson G Fujikawa
Sep 27, 2015·Neurobiology of Disease·Henrik HagbergFloris Groenendaal
May 23, 2013·Acta Physiologica·A Corcoran, J J O'Connor
Nov 8, 2014·British Journal of Pharmacology·Christine M EmnettSteven Mennerick
Apr 25, 2015·Cell Death and Differentiation·D Jimenez-BlascoJ P Bolaños
Apr 14, 2016·Neurobiology of Disease·Kashif MahfoozJohn F Wesseling
Dec 24, 2013·Progress in Neurobiology·Ted Weita LaiYu Tian Wang
Feb 5, 2014·Expert Opinion on Pharmacotherapy·Jerry J FloresJohn H Zhang
May 31, 2014·Biochimica Et Biophysica Acta·Edward D PloweyCharleen T Chu
Apr 20, 2014·Neuron·Matthew P Parsons, Lynn A Raymond
Oct 26, 2013·Progress in Neurobiology·Margarida V CaldeiraCarlos B Duarte
Sep 23, 2014·Neuropharmacology·Marianela Garcia-MunozGordon W Arbuthnott
Dec 10, 2014·Antioxidants & Redox Signaling·Lisa GasperiniGiuseppe Legname
Dec 3, 2014·Current Opinion in Pharmacology·Jon W JohnsonNadezhda V Povysheva
Jun 11, 2016·Progress in Neurobiology·Michele CurcioCarlos B Duarte
Aug 5, 2016·Nano Letters·Alex SavchenkoElena Molokanova
Oct 19, 2016·Neurobiology of Disease·Nadezhda V Povysheva, Jon W Johnson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Alexandra M KaufmanLynn A Raymond
FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
F LéveilléA Buisson
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Peng XiaS A Lipton
© 2021 Meta ULC. All rights reserved