Dendritic and mitochondrial changes during glutamate excitotoxicity

Sam M. Greenwood, Christopher N. Connolly

    Research output: Contribution to journalReview article

    83 Citations (Scopus)

    Abstract

    Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS) and is normally stored intracellularly. However, in instances of CNS injury or disease, increased concentrations of extracellular glutamate can result in the over-activation of ionotropic glutamate receptors and trigger neuronal cell death (termed excitotoxicity). Two early hallmarks of such neuronal toxicity are mitochondrial dysfunction (depolarisation, decreased ATP synthesis, structural collapse and potential opening of the permeability transition pore) and the formation of focal swellings (also termed varicosities/beads) along the length of the dendrites. In this review, we summarise current knowledge of the mechanisms that underlie these early excitotoxic events as well as the mechanisms that facilitate dendritic recovery following termination of the excitotoxic insult. (c) 2007 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)891-898
    Number of pages8
    JournalNeuropharmacology
    Volume53
    Issue number8
    DOIs
    Publication statusPublished - Dec 2007

    Keywords

    • excitotoxicity
    • glutamate
    • dendrite injury
    • beading
    • mitochondrial dysfunction
    • dendrite remodelling
    • CEREBELLAR GRANULE CELLS
    • METHYL-D-ASPARTATE
    • ACUTE HIPPOCAMPAL SLICES
    • PERMEABILITY TRANSITION
    • RECEPTOR ACTIVATION
    • TRANSGENIC MICE
    • KAINIC ACID
    • IN-VIVO
    • MEDIATED EXCITOTOXICITY
    • NEURITIC DEGENERATION

    Cite this

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    title = "Dendritic and mitochondrial changes during glutamate excitotoxicity",
    abstract = "Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS) and is normally stored intracellularly. However, in instances of CNS injury or disease, increased concentrations of extracellular glutamate can result in the over-activation of ionotropic glutamate receptors and trigger neuronal cell death (termed excitotoxicity). Two early hallmarks of such neuronal toxicity are mitochondrial dysfunction (depolarisation, decreased ATP synthesis, structural collapse and potential opening of the permeability transition pore) and the formation of focal swellings (also termed varicosities/beads) along the length of the dendrites. In this review, we summarise current knowledge of the mechanisms that underlie these early excitotoxic events as well as the mechanisms that facilitate dendritic recovery following termination of the excitotoxic insult. (c) 2007 Elsevier Ltd. All rights reserved.",
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    author = "Greenwood, {Sam M.} and Connolly, {Christopher N.}",
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    month = "12",
    doi = "10.1016/j.neuropharm.2007.10.003",
    language = "English",
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    Dendritic and mitochondrial changes during glutamate excitotoxicity. / Greenwood, Sam M.; Connolly, Christopher N.

    In: Neuropharmacology, Vol. 53, No. 8, 12.2007, p. 891-898.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - Dendritic and mitochondrial changes during glutamate excitotoxicity

    AU - Greenwood, Sam M.

    AU - Connolly, Christopher N.

    PY - 2007/12

    Y1 - 2007/12

    N2 - Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS) and is normally stored intracellularly. However, in instances of CNS injury or disease, increased concentrations of extracellular glutamate can result in the over-activation of ionotropic glutamate receptors and trigger neuronal cell death (termed excitotoxicity). Two early hallmarks of such neuronal toxicity are mitochondrial dysfunction (depolarisation, decreased ATP synthesis, structural collapse and potential opening of the permeability transition pore) and the formation of focal swellings (also termed varicosities/beads) along the length of the dendrites. In this review, we summarise current knowledge of the mechanisms that underlie these early excitotoxic events as well as the mechanisms that facilitate dendritic recovery following termination of the excitotoxic insult. (c) 2007 Elsevier Ltd. All rights reserved.

    AB - Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS) and is normally stored intracellularly. However, in instances of CNS injury or disease, increased concentrations of extracellular glutamate can result in the over-activation of ionotropic glutamate receptors and trigger neuronal cell death (termed excitotoxicity). Two early hallmarks of such neuronal toxicity are mitochondrial dysfunction (depolarisation, decreased ATP synthesis, structural collapse and potential opening of the permeability transition pore) and the formation of focal swellings (also termed varicosities/beads) along the length of the dendrites. In this review, we summarise current knowledge of the mechanisms that underlie these early excitotoxic events as well as the mechanisms that facilitate dendritic recovery following termination of the excitotoxic insult. (c) 2007 Elsevier Ltd. All rights reserved.

    KW - excitotoxicity

    KW - glutamate

    KW - dendrite injury

    KW - beading

    KW - mitochondrial dysfunction

    KW - dendrite remodelling

    KW - CEREBELLAR GRANULE CELLS

    KW - METHYL-D-ASPARTATE

    KW - ACUTE HIPPOCAMPAL SLICES

    KW - PERMEABILITY TRANSITION

    KW - RECEPTOR ACTIVATION

    KW - TRANSGENIC MICE

    KW - KAINIC ACID

    KW - IN-VIVO

    KW - MEDIATED EXCITOTOXICITY

    KW - NEURITIC DEGENERATION

    U2 - 10.1016/j.neuropharm.2007.10.003

    DO - 10.1016/j.neuropharm.2007.10.003

    M3 - Review article

    VL - 53

    SP - 891

    EP - 898

    JO - Neuropharmacology

    JF - Neuropharmacology

    SN - 0028-3908

    IS - 8

    ER -