Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices

Authors

  • Takahiro Takano,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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    • Takahiro Takano, Wei He and Xiaoning Han contributed equally to the work

  • Wei He,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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    • Takahiro Takano, Wei He and Xiaoning Han contributed equally to the work

  • Xiaoning Han,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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    • Takahiro Takano, Wei He and Xiaoning Han contributed equally to the work

  • Fushun Wang,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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  • Qiwu Xu,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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  • Xiaohai Wang,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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  • Nancy Ann Oberheim Bush,

    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
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  • Nancy Cruz,

    1. Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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  • Gerald A. Dienel,

    1. Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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  • Maiken Nedergaard

    Corresponding author
    1. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York
    • Address correspondence to Maiken Nedergaard; Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA. E-mail: Nedergaard@urmc.rochester.edu

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Abstract

A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here showed that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from glial fibrillary acidic protein-green fluorescent protein reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field excitatory postsynaptic current. Analysis of Ca2+ signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice versus in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. GLIA 2013;62:78–95

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