Elsevier

Brain Research

Volume 588, Issue 1, 14 August 1992, Pages 154-158
Brain Research

Short communication
Corticosterone accelerates hypoxia- and cyanide-induced ATP loss in cultured hippocampal astrocytes

https://doi.org/10.1016/0006-8993(92)91356-JGet rights and content

Abstract

Glucocorticoids potentiate injury to the rodent hippocampus following a variety of metabolic insults, including hypoxia/ischemia, both in vitro and in vivo. We have examined whether corticosterone (CORT), the principal glucocorticoid in the rat, could exacerbate hypoxic energy failure in cultured hippocampal astrocytes. Exposure to 6 h of atmospheric hypoxia (100% N2) or to 30 min of cyanide did not cause any detectable cell injury, although moderate astrocyte damage did occur alter 6 h of hypoxia in the absence of glucose. Both cyanide and hypoxia significantly reduced astrocyte ATP content, a decline that was further reduced when glucose was omitted. A 30 min exposure to 100 μM glutamate elevated ATP content under normoxic conditions but enhanced the cyanide-induced loss of ATP. A 24 h pre-treatment with CORT did not influence normoxic ATP levels but potentiated the loss of ATP following both cyanide and hypoxia. CORT also exacerbated the loss of ATP seen after combined exposure to cyanide and glutamate, as well as that following cyanide + 0 mM glucose. These results indicate that both CORT and glutamate can potentiate hypoxia-induced energy failure in hippocampal astrocytes, albeit by different mechanisms.

References (41)

  • C.L. Bowman et al.

    Excitatory amino acids directly depolarize rat brain astrocytes in primary culture

    Nature

    (1984)
  • A. Caceres et al.

    Immunocytochemical localization of tubulin and microtubule-associated protein 2 during the development of hippocampal neurons in culture

    J. Neurosci.

    (1986)
  • J.A. Conner et al.

    Sustained dendritic gradients of Ca2+ induced by excitatory amino acids in CA1 hippocampal neurons

    Science

    (1988)
  • A.H. Cornell-Bell et al.

    Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling

    Science

    (1990)
  • M.F. Dallman et al.

    Characterization of corticosterone feedback regulation of ACTH secretion

  • J.M. Dubinsky et al.

    Intracellular calcium concentrations during ‘chemical hypoxia’ and excitotoxic neuronal injury

    J. Neurosci.

    (1991)
  • Elliott, E.M., Chang, I.J. and Sapolsky, R.M., Corticosterone enhances kainic acid-induced calcium mobilization in...
  • M. Erecinska et al.

    ATP and brain function

    J. Cereb. Blood Flow Metab.

    (1989)
  • R.S. Goldman

    Role of intracellular calcium in hypoxic/ischemic injury in cultured astrocytes

    Soc. Neurosci. Abstr.

    (1991)
  • L. Hertz et al.

    Energy metabolism in glutamatergic neurons, GABAergic neurons and astrocytes in primary cultures

    Neurochem. Res.

    (1988)
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    We thank Desta Packan and Sheila Brooke for expert technical assistance and Dr. Kate Raley-Susman for helpful comments. Support was provided to R.M.S. by the National Institute on Aging (AG06633) and by a Presidential Young Investigators Award, and to G.C.T. by a pre-doctoral fellowship from the National Science Foundation.

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