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PMID: 15126684 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Hydrogen peroxide as a diffusible signal molecule in synaptic plasticity.

Molecular neurobiology ·Vol. 29 ·No. 2 ·2004-04-00 ·Pages 167-78

Kamsler A, Segal M

Abstract

Reactive oxygen species (ROS) have been considered for some time only in the context of oxidative stress-induced cell damage. In this review, we discuss the growing body of evidence that implicates ROS in general, and hydrogen peroxide (H2O2) in particular, in regulatory events underlying synaptic plasticity. H2O2 is regarded in this context as a specific diffusible signaling molecule. The action of H2O2 is assumed to be carried out via the release of calcium ions from internal stores, modulating the activity of specific calcium-dependent protein phosphatases. These phosphatases eventually affect neuronal plasticity. We discuss the role of H2O2 in these systems, stressing the importance of cellular regulation of H2O2 levels that are altered in aging individuals, in the ability to express plasticity. These studies highlight the function of H2O2 in processes of learning and memory and their change in elderly individuals, irrespective of neurodegeneration found in Alzheimer's patients.

MeSH Terms
Animals Diffusion Excitatory Postsynaptic Potentials/physiology Humans Hydrogen Peroxide/metabolism Neuronal Plasticity/physiology Reactive Oxygen Species/metabolism Signal Transduction/physiology Synapses/metabolism
Chemicals
Reactive Oxygen Species Hydrogen Peroxide
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kamsler Ariel
Department of Neurobiology, The Weizmann Institute, Rehovot, 76100 Israel. ariel.kamsler@weizmann.ac.il
Segal Menahem
References (71)
71 references, click to expand
  1. Hydrogen peroxide modulation of synaptic plasticity.
    J Neurosci. 2003 Jan 1;23(1):269-76 PMID: 12514224
  2. Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria.
    Free Radic Biol Med. 2002 May 1;32(9):882-9 PMID: 11978489
  3. Age-related impairment in LTP is accompanied by enhanced activity of stress-activated protein kinases: analysis of underlying mechanisms.
    Eur J Neurosci. 2000 Jan;12(1):345-52 PMID: 10651889
  4. Premature aging changes in neuromuscular junctions of transgenic mice with an extra human CuZnSOD gene: a model for tongue pathology in Down's syndrome.
    J Neurol Sci. 1988 Dec;88(1-3):41-53 PMID: 2976083
  5. Hydrogen peroxide induces contraction and raises [Ca2+]i in canine cerebral arterial smooth muscle: participation of cellular signaling pathways.
    Naunyn Schmiedebergs Arch Pharmacol. 1999 Dec;360(6):646-53 PMID: 10619181
  6. Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells.
    Mutat Res. 2001 Sep 20;496(1-2):181-90 PMID: 11551494
  7. Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids.
    Neuroscience. 1999;94(1):305-14 PMID: 10613520
  8. Hydrogen peroxide induces intracellular calcium overload by activation of a non-selective cation channel in an insulin-secreting cell line.
    J Biol Chem. 1999 Jan 8;274(2):833-41 PMID: 9873022
  9. Transient Ca2+ changes in endothelial cells induced by low doses of reactive oxygen species: role of hydrogen peroxide.
    Mol Cell Biochem. 1997 Jun;171(1-2):11-21 PMID: 9201690
  10. Exposure to hydrogen peroxide induces cell death via apoptosis in primary cultured mouse hepatocytes.
    Biol Pharm Bull. 1999 Dec;22(12):1296-300 PMID: 10746159
  11. NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices.
    J Neurophysiol. 2002 Jun;87(6):2896-903 PMID: 12037193
  12. A role for superoxide in protein kinase C activation and induction of long-term potentiation.
    J Biol Chem. 1998 Feb 20;273(8):4516-22 PMID: 9468506
  13. Calcineurin links Ca2+ dysregulation with brain aging.
    J Neurosci. 2001 Jun 1;21(11):4066-73 PMID: 11356894
  14. Diverse effects of hydrogen peroxide on cytosolic Ca2+ homeostasis in rat pancreatic beta-cells.
    Cell Struct Funct. 2000 Jun;25(3):187-93 PMID: 10984102
  15. Measurement of striatal H2O2 by microdialysis following global forebrain ischemia and reperfusion in the rat: correlation with the cytotoxic potential of H2O2 in vitro.
    Brain Res. 1995 Feb 13;671(2):181-6 PMID: 7743206
  16. Measurement of the extracellular H2O2 in the brain by microdialysis.
    Brain Res Brain Res Protoc. 1998 Sep;3(1):33-6 PMID: 9767095
  17. NMDA-dependent superoxide production and neurotoxicity.
    Nature. 1993 Aug 5;364(6437):535-7 PMID: 7687749
  18. Phosphorylation of presynaptic and postsynaptic calcium channels by cAMP-dependent protein kinase in hippocampal neurons.
    EMBO J. 1995 Jul 3;14(13):3036-44 PMID: 7621818
  19. Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels.
    J Neurosci. 1998 May 1;18(9):3171-9 PMID: 9547225
  20. Phosphatidic acid-induced elevation of intracellular Ca2+ is mediated by RhoA and H2O2 in Rat-2 fibroblasts.
    J Biol Chem. 1998 May 22;273(21):12710-5 PMID: 9582294
  21. Reactive oxygen species and the central nervous system.
    J Neurochem. 1992 Nov;59(5):1609-23 PMID: 1402908
  22. Hydrogen peroxide-mediated phosphorylation of ERK1/2, Akt/PKB and JNK in cortical neurones: dependence on Ca(2+) and PI3-kinase.
    J Neurochem. 2002 Jan;80(1):24-35 PMID: 11796740
  23. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid.
    Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61 PMID: 11854529
  24. H2O2 enhances Ca2+ release from osteoblast internal stores.
    Yonsei Med J. 2002 Apr;43(2):229-35 PMID: 11971217
  25. Alterations in the balance of protein kinase/phosphatase activities parallel reduced synaptic strength during aging.
    J Neurophysiol. 1998 Sep;80(3):1567-70 PMID: 9744962
  26. Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C.
    J Neurosci. 2002 Feb 1;22(3):674-83 PMID: 11826097
  27. Severity of oxidative stress generates different mechanisms of endothelial cell death.
    Cell Tissue Res. 2001 Dec;306(3):409-16 PMID: 11735041
  28. Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling.
    Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):448-53 PMID: 10618438
  29. Impairment of long-term potentiation and associative memory in mice that overexpress extracellular superoxide dismutase.
    J Neurosci. 2000 Oct 15;20(20):7631-9 PMID: 11027223
  30. A synaptic model of memory: long-term potentiation in the hippocampus.
    Nature. 1993 Jan 7;361(6407):31-9 PMID: 8421494
  31. Semantic memory and the human hippocampus.
    Neuron. 2003 Apr 10;38(1):127-33 PMID: 12691670
  32. Evidence that interleukin-1beta and reactive oxygen species production play a pivotal role in stress-induced impairment of LTP in the rat dentate gyrus.
    Eur J Neurosci. 2001 Dec;14(11):1809-19 PMID: 11860476
  33. CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression.
    Cell. 1996 Dec 27;87(7):1203-14 PMID: 8980227
  34. Inactivation of calcineurin by hydrogen peroxide and phenylarsine oxide. Evidence for a dithiol-disulfide equilibrium and implications for redox regulation.
    Eur J Biochem. 2000 Mar;267(5):1407-15 PMID: 10691978
  35. Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory.
    Cell. 2001 Nov 30;107(5):617-29 PMID: 11733061
  36. Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.
    EMBO J. 1995 Oct 16;14(20):4985-93 PMID: 7588627
  37. Calcineurin enhances L-type Ca(2+) channel activity in hippocampal neurons: increased effect with age in culture.
    Neuroscience. 2002;110(2):213-25 PMID: 11958864
  38. Inducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin.
    Cell. 2001 Mar 9;104(5):675-86 PMID: 11257222
  39. Postsynaptic protein phosphorylation and LTP.
    Trends Neurosci. 2000 Feb;23(2):75-80 PMID: 10652548
  40. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):8044-8 PMID: 2960971
  41. Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11158-62 PMID: 1763030
  42. Peroxide modulation of slow onset potentiation in rat hippocampus.
    J Neurosci. 1997 Nov 15;17(22):8695-701 PMID: 9348338
  43. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363-7 PMID: 1350090
  44. Modulation of protein kinases and protein phosphatases by reactive oxygen species: implications for hippocampal synaptic plasticity.
    Prog Neuropsychopharmacol Biol Psychiatry. 1999 Apr;23(3):359-76 PMID: 10378223
  45. Are reactive oxygen species involved in Alzheimer's disease?
    Neurobiol Aging. 1995 Jul-Aug;16(4):661-74 PMID: 8544918
  46. A calcineurin inhibitor, FK506, blocks voltage-gated calcium channel-dependent LTP in the hippocampus.
    Neurosci Res. 1998 Apr;30(4):313-9 PMID: 9678635
  47. Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity.
    J Neurosci. 2001 Dec 15;21(24):9744-56 PMID: 11739583
  48. Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1.
    J Neurophysiol. 1998 Jul;80(1):452-7 PMID: 9658063
  49. Overexpression of copper/zinc superoxide dismutase in transgenic mice protects against neuronal cell death after transient focal ischemia by blocking activation of the Bad cell death signaling pathway.
    J Neurosci. 2003 Mar 1;23(5):1710-8 PMID: 12629175
  50. Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin.
    Cell. 1998 Jan 9;92 (1):25-37 PMID: 9489697
  51. Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus.
    Neuroscience. 1991;44(2):353-9 PMID: 1658680
  52. Postsynaptic calcineurin activity downregulates synaptic transmission by weakening intracellular Ca2+ signaling mechanisms in hippocampal CA1 neurons.
    J Neurosci. 1997 Jun 15;17(12):4600-11 PMID: 9169521
  53. Superoxide dismutase and the death of motoneurons in ALS.
    Trends Neurosci. 2001 Nov;24(11 Suppl):S15-20 PMID: 11881740
  54. The free radical theory of aging matures.
    Physiol Rev. 1998 Apr;78(2):547-81 PMID: 9562038
  55. Critical dependence of cAMP response element-binding protein phosphorylation on L-type calcium channels supports a selective response to EPSPs in preference to action potentials.
    J Neurosci. 2000 Jan 1;20(1):266-73 PMID: 10627604
  56. Effect of hydrogen peroxide on calcium homeostasis in smooth muscle cells.
    Arch Biochem Biophys. 1992 Sep;297(2):265-70 PMID: 1497346
  57. Reversible impairment of long-term potentiation in transgenic Cu/Zn-SOD mice.
    Eur J Neurosci. 1998 Feb;10(2):538-44 PMID: 9749716
  58. The A-kinase anchor protein MAP2B and cAMP-dependent protein kinase are associated with class C L-type calcium channels in neurons.
    J Biol Chem. 1999 Oct 15;274(42):30280-7 PMID: 10514522
  59. Paradoxical actions of hydrogen peroxide on long-term potentiation in transgenic superoxide dismutase-1 mice.
    J Neurosci. 2003 Nov 12;23 (32):10359-67 PMID: 14614095
  60. Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease.
    J Biol Chem. 2001 Oct 19;276(42):38787-94 PMID: 11483593
  61. Involvement of hydrogen peroxide in asbestos-induced NFAT activation.
    Mol Cell Biochem. 2002 May-Jun;234-235(1-2):161-8 PMID: 12162429
  62. VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo.
    J Neurophysiol. 1999 Aug;82(2):736-40 PMID: 10444671
  63. Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons.
    J Neurosci. 1996 Oct 1;16(19):6286-95 PMID: 8815908
  64. Vanadium-induced nuclear factor of activated T cells activation through hydrogen peroxide.
    J Biol Chem. 2001 Jun 22;276(25):22397-403 PMID: 11292823
  65. Role of voltage-dependent calcium channel long-term potentiation (LTP) and NMDA LTP in spatial memory.
    J Neurosci. 2000 Dec 15;20(24):9272-6 PMID: 11125005
  66. Hydrogen peroxide activation of multiple mitogen-activated protein kinases in an oligodendrocyte cell line: role of extracellular signal-regulated kinase in hydrogen peroxide-induced cell death.
    J Neurochem. 1999 Jan;72 (1):112-9 PMID: 9886061
  67. Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation.
    J Neurosci. 2002 Jan 1;22(1):209-17 PMID: 11756504
  68. Mechanisms of Ca2+ overload induced by extracellular H2O2 in quiescent isolated rat cardiomyocytes.
    Basic Res Cardiol. 2001 Nov;96(6):623-9 PMID: 11770081
  69. Mechanisms underlying H(2)O(2)-mediated inhibition of synaptic transmission in rat hippocampal slices.
    Brain Res. 2000 Nov 3;882(1-2):86-94 PMID: 11056187
  70. p53 dependent apoptosis in glioma cell lines in response to hydrogen peroxide induced oxidative stress.
    Int J Biochem Cell Biol. 2002 Feb;34(2):148-57 PMID: 11809417
  71. Upregulation of GABA neurotransmission suppresses hippocampal excitability and prevents long-term potentiation in transgenic superoxide dismutase-overexpressing mice.
    J Neurosci. 1999 Dec 15;19(24):10977-84 PMID: 10594078
Article Info
Journal
Molecular neurobiology
Abbr.
Mol Neurobiol
ISSN
0893-7648
DOI
10.1385/MN:29:2:167
Email
ariel.kamsler@weizmann.ac.il
Published
2004-04-00
Pages
167-78
Language
English
Region
United States
NLM ID
8900963
Subset
IM
External Links
PubMed source DOI: 10.1385/MN:29:2:167 View journal details
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