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Alzheimer’s amyloid β-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes

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Abstract

Alzheimer’s disease (AD) involves the progressive extracellular deposition of amyloid β-peptide (Aβ), a self-aggregating 40–42 amino acid protein that can damage neurons resulting in their dysfunction and death. Studies of neurons have shown that Aβ perturbs cellular-calcium homeostasis so that calcium responses to agonists that induce calcium influx or release from internal stores are increased. The recent discovery of intercellular calcium waves in astrocytes suggests intriguing roles for astrocytes in the long-range transfer of information in the nervous system. We now report that Aβ alters calcium-wave signaling in cultured rat cortical astrocytes. Exposure of astrocytes to Aβ1-42 resulted in an increase in the amplitude and velocity of evoked calcium waves, and increased the distance the waves traveled. Suramin decreased wave propagation in untreated astrocytes and abrogated the enhancing effect of Aβ on calcium-wave amplitude and velocity, indicating a requirement for extracellular ATP in wave propagation. Treatment of astrocytes with an uncoupler of gap junctions did not significantly reduce the amplitude, velocity, or distance of calcium waves in control cultures, but completely abolished the effects of Aβ on each of the three wave parameters. These findings reveal a novel action of Aβ on the propagation of intercellular calcium signals in astrocytes, and also suggests a role for altered astrocyte calcium-signaling in the pathogenesis of AD.

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Authors and Affiliations

  1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, 21224, Baltimore, MD

    Norman J. Haughey & Mark P. Mattson

  2. Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, 21287, Baltimore, MD

    Norman J. Haughey

  3. Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, 21205, Baltimore, MD

    Mark P. Mattson

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  1. Norman J. Haughey
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  2. Mark P. Mattson
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Correspondence to Mark P. Mattson.

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Haughey, N.J., Mattson, M.P. Alzheimer’s amyloid β-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes. Neuromol Med 3, 173–180 (2003). https://doi.org/10.1385/NMM:3:3:173

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  • DOI: https://doi.org/10.1385/NMM:3:3:173

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