Striatal neurones show sustained recovery from severe hypoglycaemic insult

Authors

  • C. J. McDermott,

    1. Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
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    • 1

      The present address of C. J. McDermott is 15–403 College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.

  • K. N. Bradley,

    1. Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
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  • J. G. McCarron,

    1. Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
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  • A. M. Palmer,

    1. Vernalis plc, Winnersh, Berkshire, UK
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  • B. J. Morris

    1. Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
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Address correspondence and reprint requests to B. J. Morris, Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, Scotland G12 8QQ. E-mail: B.Morris@bio.gla.ac.uk

Abstract

Glucose deprivation provides a reliable model to investigate cellular responses to metabolic dysfunction, and is reportedly associated with permanent cell death in many paradigms. Consistent with previous studies, primary cultures of rat striatal neurones exposed to 24-h hypoglycaemia showed dramatically decreased sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) metabolism (used as a marker of cell viability) and increased TUNEL staining, suggesting widespread DNA damage typical of apoptotic cell death. Remarkably, restoration of normal glucose levels initiated a sustained recovery in XTT staining, along with a concomitant decrease in TUNEL staining, even after 24 h of hypoglycaemia, suggesting recovery of damaged neurones and repair of nicked DNA. No alterations in the levels of four DNA repair proteins could be detected during hypoglycaemia or recovery. A reduction in intracellular calcium concentration was seen in recovered cells. These data suggest that striatal cells do not die after extended periods of glucose deprivation, but survive in a form of suspended animation, with sufficient energy to maintain membrane potential.

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