G E Hardingham

Summary

Affiliation: University of Edinburgh
Country: UK

Publications

  1. ncbi request reprint Coupling of extrasynaptic NMDA receptors to a CREB shut-off pathway is developmentally regulated
    Giles E Hardingham
    Department of Preclinical Veterinary Sciences, Royal Dick School of Veterinary Studies, Edinburgh University, Summerhall, EH9 1QH, Edinburgh, UK
    Biochim Biophys Acta 1600:148-53. 2002
  2. pmc 2B synaptic or extrasynaptic determines signalling from the NMDA receptor
    Giles E Hardingham
    Centre for Neuroscience Research, University of Edinburgh, Summerhall Square, Edinburgh EH9 1QH, UK
    J Physiol 572:614-5. 2006
  3. pmc Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms
    K Gupta
    Euan MacDonald Centre, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
    Cell Death Differ 19:779-87. 2012
  4. pmc Recovery of NMDA receptor currents from MK-801 blockade is accelerated by Mg2+ and memantine under conditions of agonist exposure
    Sean McKay
    Centre for Integrative Physiology, University of Edinburgh School of Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
    Neuropharmacology 74:119-25. 2013
  5. pmc Excitotoxic insults lead to peroxiredoxin hyperoxidation
    Frederic Leveille
    Center for Integrative Physiology, University of Edinburgh, Edinburgh, UK
    Oxid Med Cell Longev 2:110-3. 2009
  6. pmc Pituitary adenylate cyclase-activating peptide induces long-lasting neuroprotection through the induction of activity-dependent signaling via the cyclic AMP response element-binding protein-regulated transcription co-activator 1
    Paul S Baxter
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK
    J Neurochem 118:365-78. 2011
  7. pmc Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
    Kunal Gupta
    Anne McLaren Laboratory for Regenerative Medicine and Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SZ, UK
    Br J Clin Pharmacol 75:907-18. 2013
  8. pmc In cortical neurons HDAC3 activity suppresses RD4-dependent SMRT export
    Francesc X Soriano
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom
    PLoS ONE 6:e21056. 2011
  9. pmc Activation of Nrf2-regulated glutathione pathway genes by ischemic preconditioning
    Karen F S Bell
    Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, UK
    Oxid Med Cell Longev 2011:689524. 2011
  10. pmc The subtype of GluN2 C-terminal domain determines the response to excitotoxic insults
    Marc Andre Martel
    Centre for Integrative Physiology, University of Edinburgh School of Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
    Neuron 74:543-56. 2012

Collaborators

Detail Information

Publications39

  1. ncbi request reprint Coupling of extrasynaptic NMDA receptors to a CREB shut-off pathway is developmentally regulated
    Giles E Hardingham
    Department of Preclinical Veterinary Sciences, Royal Dick School of Veterinary Studies, Edinburgh University, Summerhall, EH9 1QH, Edinburgh, UK
    Biochim Biophys Acta 1600:148-53. 2002
    ....
  2. pmc 2B synaptic or extrasynaptic determines signalling from the NMDA receptor
    Giles E Hardingham
    Centre for Neuroscience Research, University of Edinburgh, Summerhall Square, Edinburgh EH9 1QH, UK
    J Physiol 572:614-5. 2006
  3. pmc Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms
    K Gupta
    Euan MacDonald Centre, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
    Cell Death Differ 19:779-87. 2012
    ..Thus, human astrocytes can mediate neuroprotection through glutathione-dependent and glutathione-independent mechanisms, and represent a therapeutic target for human disorders associated with neuronal oxidative stress...
  4. pmc Recovery of NMDA receptor currents from MK-801 blockade is accelerated by Mg2+ and memantine under conditions of agonist exposure
    Sean McKay
    Centre for Integrative Physiology, University of Edinburgh School of Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
    Neuropharmacology 74:119-25. 2013
    ..This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. ..
  5. pmc Excitotoxic insults lead to peroxiredoxin hyperoxidation
    Frederic Leveille
    Center for Integrative Physiology, University of Edinburgh, Edinburgh, UK
    Oxid Med Cell Longev 2:110-3. 2009
    ..Thus, the effect of NMDA receptor activity on the activity of neuronal peroxiredoxins follows the classical U-shaped dose response curve...
  6. pmc Pituitary adenylate cyclase-activating peptide induces long-lasting neuroprotection through the induction of activity-dependent signaling via the cyclic AMP response element-binding protein-regulated transcription co-activator 1
    Paul S Baxter
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK
    J Neurochem 118:365-78. 2011
    ..Thus, the enhancement of AP firing may play a significant role in the neuroprotective actions of PACAP and other adenylate cyclase-coupled ligands...
  7. pmc Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
    Kunal Gupta
    Anne McLaren Laboratory for Regenerative Medicine and Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SZ, UK
    Br J Clin Pharmacol 75:907-18. 2013
    ....
  8. pmc In cortical neurons HDAC3 activity suppresses RD4-dependent SMRT export
    Francesc X Soriano
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom
    PLoS ONE 6:e21056. 2011
    ..Furthermore, they underline the fact that HDAC inhibitors can cause reorganization and redistribution of corepressor complexes...
  9. pmc Activation of Nrf2-regulated glutathione pathway genes by ischemic preconditioning
    Karen F S Bell
    Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, UK
    Oxid Med Cell Longev 2011:689524. 2011
    ..Taken together, these studies indicate that astrocytic Nrf2 may represent an important mediator of endogenous neuroprotective preconditioning pathways...
  10. pmc The subtype of GluN2 C-terminal domain determines the response to excitotoxic insults
    Marc Andre Martel
    Centre for Integrative Physiology, University of Edinburgh School of Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
    Neuron 74:543-56. 2012
    ..Dependence of NMDAR excitotoxicity on the GluN2 CTD subtype can be overcome by inducing high levels of NMDAR activity. Thus, the identity (2A versus 2B) of the GluN2 CTD controls the toxicity dose-response to episodes of NMDAR activity...
  11. pmc Pro-survival signalling from the NMDA receptor
    G E Hardingham
    Centre for Neuroscience Research, University of Edinburgh, Summerhall Square, Edinburgh EH9 1QH, UK
    Biochem Soc Trans 34:936-8. 2006
    ..Understanding the mechanisms that underlie these opposing effects may lead to strategies to selectively block pro-death signalling, which could have considerable clinical benefits...
  12. doi request reprint Regulation of neuronal oxidative and nitrosative stress by endogenous protective pathways and disease processes
    Giles E Hardingham
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom
    Antioxid Redox Signal 14:1421-4. 2011
    ..Such approaches offer an alternative strategy to classical antioxidant interventions based on the administration of free radical scavengers and spin-traps...
  13. pmc Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders
    Giles E Hardingham
    Centre for Integrative Physiology, University of Edinburgh, School of Biomedical Sciences, Hugh Robson Building, Edinburgh EH8 9XD, UK
    Nat Rev Neurosci 11:682-96. 2010
    ..Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling...
  14. pmc Human embryonic stem cell-derived neurons as a tool for studying neuroprotection and neurodegeneration
    Giles E Hardingham
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH89XD, UK
    Mol Neurobiol 42:97-102. 2010
    ....
  15. pmc TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner
    S Edman
    Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
    Neuropharmacology 63:441-9. 2012
    ..Nevertheless, while TCN 201 is a potent antagonist it must be borne in mind that its ability to block GluN2A-containing NMDARs is dependent on the GluN1-agonist concentration and is limited by its low solubility...
  16. pmc In developing hippocampal neurons, NR2B-containing N-methyl-D-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death
    M A Martel
    Centre for Neuroscience Research, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh EH8 9XD, UK
    Neuroscience 158:334-43. 2009
    ..In this instance, subunit differences cannot account for the dichotomous nature of NMDA receptor signaling...
  17. pmc Direct pharmacological monitoring of the developmental switch in NMDA receptor subunit composition using TCN 213, a GluN2A-selective, glycine-dependent antagonist
    S McKay
    Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, UK
    Br J Pharmacol 166:924-37. 2012
    ..Here we use TCN 213, a novel GluN2A-selective antagonist to identify the presence of this subunit in functional NMDA receptors in developing cortical neurones...
  18. pmc Influence of GluN2 subunit identity on NMDA receptor function
    D J A Wyllie
    Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
    Neuropharmacology 74:4-17. 2013
    ..This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. ..
  19. ncbi request reprint Nuclear Ca2+ and the cAMP response element-binding protein family mediate a late phase of activity-dependent neuroprotection
    Sofia Papadia
    Centre for Neuroscience Research, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom
    J Neurosci 25:4279-87. 2005
    ..Thus, activity-dependent neuroprotection comprises two mechanistically distinct phases that differ in their spatial requirements for calcium and in their reliance on the CREB family...
  20. ncbi request reprint Inhibiting pro-death NMDA receptor signaling dependent on the NR2 PDZ ligand may not affect synaptic function or synaptic NMDA receptor signaling to gene expression
    Marc Andre Martel
    Center for Integrative Physiology, University of Edinburgh, Edinburgh, UK
    Channels (Austin) 3:12-5. 2009
    ..Thus, while the NR2 PDZ ligand does not account for all the excitotoxic effects of excessive NMDAR activity, these findings underline the value of the specific targeting of death pathways downstream of the NMDAR...
  21. pmc Coupling of the NMDA receptor to neuroprotective and neurodestructive events
    Giles E Hardingham
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK
    Biochem Soc Trans 37:1147-60. 2009
    ..Increased understanding in this field is leading to the discovery of new therapeutic targets and strategies for excitotoxic disorders, as well as a growing appreciation of the harmful consequences of NMDA receptor blockade...
  22. ncbi request reprint The Yin and Yang of NMDA receptor signalling
    Giles E Hardingham
    Department of Preclinical Veterinary Sciences, Royal School of Veterinary Studies, Edinburgh University, Summerhall, UK
    Trends Neurosci 26:81-9. 2003
    ....
  23. pmc SynGAP isoforms exert opposing effects on synaptic strength
    A C McMahon
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK
    Nat Commun 3:900. 2012
    ..Furthermore, the direction and degree of synaptic modulation exerted by different protein isoforms from a single gene locus is dependent on the combination of differential promoter usage and alternative splicing...
  24. pmc Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability
    Francesc X Soriano
    Centre for Neuroscience Research, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom
    J Neurosci 26:4509-18. 2006
    ....
  25. pmc Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses
    Sofia Papadia
    Centre for Neuroscience Research, University of Edinburgh, Hugh Robson Building George Square, Edinburgh EH8 9XD, UK
    Nat Neurosci 11:476-87. 2008
    ..Thus, synaptic NMDAR activity may influence the progression of pathological processes associated with oxidative damage...
  26. pmc Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state
    R Patani
    Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge CB2 0SZ, UK
    Nat Commun 2:214. 2011
    ....
  27. doi request reprint NMDA receptor expression and activity in osteoarthritic human articular chondrocytes
    L Ramage
    Centre for Inflammation Research, The Queens Medical Research Institute, The University of Edinburgh, Edinburgh, UK
    Osteoarthritis Cartilage 16:1576-84. 2008
    ..This study looks at expression and activity of the ionotropic glutamate NMDA (N-methyl-D-aspartic acid) receptor (NMDAR) in human osteoarthritic (OA) chondrocytes...
  28. pmc Synaptic NMDAR activity suppresses FOXO1 expression via a cis-acting FOXO binding site: FOXO1 is a FOXO target gene
    Bashayer Al-Mubarak
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK
    Channels (Austin) 3:233-8. 2009
    ..These results suggest that FOXO-inactivating signals are likely to result in longer-term inhibition of FOXO target gene expression than previously thought...
  29. pmc Compartmentalized NMDA receptor signalling to survival and death
    Francesc X Soriano
    Centre for Neuroscience Research, University of Edinburgh, Edinburgh EH8 9XD, UK
    J Physiol 584:381-7. 2007
    ..A greater understanding of these issues may point to ways of selectively blocking pro-death signalling in neurological disorders such as stroke, where global NMDA receptor antagonists have proved ineffective...
  30. pmc Induction of sulfiredoxin expression and reduction of peroxiredoxin hyperoxidation by the neuroprotective Nrf2 activator 3H-1,2-dithiole-3-thione
    Francesc X Soriano
    Centre for Neuroscience Research, University of Edinburgh, Edinburgh, UK
    J Neurochem 107:533-43. 2008
    ....
  31. pmc Suppression of the intrinsic apoptosis pathway by synaptic activity
    Frederic Leveille
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK
    J Neurosci 30:2623-35. 2010
    ..Thus, suppression of apoptotic gene expression may synergize with other activity-dependent events such as enhancement of antioxidant defenses to promote neuronal survival...
  32. pmc The dichotomy of NMDA receptor signaling
    Sofia Papadia
    Centre for Neuroscience Research, University of Edinburgh, Edinburgh, United Kingdom
    Neuroscientist 13:572-9. 2007
    ..This knowledge may lead to therapeutic strategies that enable the selective blockade of prodeath signaling cassettes while sparing physiological signaling to survival and plasticity...
  33. pmc Role of histone acetylation in the activity-dependent regulation of sulfiredoxin and sestrin 2
    Francesc X Soriano
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Sct, UK
    Epigenetics 4:152-8. 2009
    ..Our results indicate that manipulating the histone acetylase-deacetylase balance in neurons may mimic the effects of synaptic activity in preventing the oxidative inactivation of peroxiredoxins...
  34. pmc Specific targeting of pro-death NMDA receptor signals with differing reliance on the NR2B PDZ ligand
    Francesc X Soriano
    Centres for Integrative Physiology and Neuroscience Research, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom
    J Neurosci 28:10696-710. 2008
    ..Thus, NMDAR-activated signals comprise pro-death pathways with differing requirements for PDZ protein interactions. These signals are amenable to selective inhibition, while sparing synaptic plasticity and prosurvival signaling...
  35. ncbi request reprint Nuclear Ca2+ and CaM kinase IV specify hormonal- and Notch-responsiveness
    Grahame J McKenzie
    Lorantis Ltd, Cambridge, UK
    J Neurochem 93:171-85. 2005
    ..Thus, the synaptically controlled kinase-phosphatase balance of the neuron determines the efficacy of SMRT-mediated repression and the signal-responsiveness of a variety of transcription factors...
  36. ncbi request reprint Synaptic activity induces signalling to CREB without increasing global levels of cAMP in hippocampal neurons
    Anna Pokorska
    MRC Laboratory of Molecular Biology, Division of Neurobiology, Hills Road, Cambridge, UK
    J Neurochem 84:447-52. 2003
    ....
  37. ncbi request reprint Extracellular calcium regulates postsynaptic efficacy through group 1 metabotropic glutamate receptors
    Neil R Hardingham
    The University Laboratory of Physiology, Oxford University, Oxford OX1 3PT, United Kingdom
    J Neurosci 26:6337-45. 2006
    ..Therefore, physiologically relevant changes in extracellular Ca2+ can regulate information transfer at cortical synapses via both presynaptic and postsynaptic mechanisms...
  38. ncbi request reprint Presynaptic efficacy directs normalization of synaptic strength in layer 2/3 rat neocortex after paired activity
    Neil R Hardingham
    The University Laboratory of Physiology, Oxford University, Oxford, UK
    J Neurophysiol 97:2965-75. 2007
    ..This may represent a means by which distal synapses preferentially increase their efficacy to achieve equal weighting at the soma. Paired activity thus acts to normalize synaptic strength, by both pre- and postsynaptic mechanisms...
  39. pmc Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals
    Grahame McKenzie
    Lorantis Ltd, Cambridge, CB4 0PE, UK
    BMC Cell Biol 7:10. 2006
    ..Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways...