17 Beta-oestradiol attenuates dexamethasone-induced lethal and sublethal neuronal damage in the striatum and hippocampus

LE Haynes, Corinne Lendon, David Barber, Ian Mitchell

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Abnormal corticosteroid release is extensively associated with mood disorders. This association may result from the toxic actions of endogenous corticosteroids which can induce apoptosis of hippocampal neurons. Similarly, dexamethasone, a synthetic corticosteroid, can induce lethal and sublethal damage to rat hippocampal and striatal neurons and can result in steroid-induced psychoses in humans. The experiments reported here tested the hypothesis that pre-treatment with oestrogen would also attenuate dexamethasone-induced neuronal damage as oestrogens have neuroprotective actions against a variety of insults and falling levels of oestrogen are associated with increased vulnerability to mood disorders. Male Sprague-Dawley rats received three systemic injections which were a combination of vehicle, 17-beta-oestradiol (0.2 mg/kg, s.c.), the oestrogen receptor antagonist tamoxifen (10 mg/kg, s.c.) and dexamethasone (0.7 mg/kg, i.p.) and were killed 24 h after the final injection. Injections of dexamethasone (when preceded by vehicle injections) resulted in elevated levels of apoptosis and sub-lethal damage, as demonstrated by reduced levels of microtubule-associated protein-2-immunopositive neurons, in the striatum and hippocampus. This damage was regional with the dorsomedial caudate putamen and the dentate gyrus and CA1 and CA3 hippocampal sub-fields being particularly affected. Pretreatment with oestrogen substantially attenuated the dexamethasone-induced neuronal damage. This oestrogen-induced neuronal protection was in turn virtually eliminated by giving an initial injection of tamoxifen. These results suggest, therefore, that oestrogens can protect from corticosteroid-induced neuronal damage via an oestrogen receptor-mediated process.
Original languageEnglish
Pages (from-to)799-806
Number of pages8
JournalNeuroscience
Volume120
Issue number3
DOIs
Publication statusPublished - 1 Sep 2003

Keywords

  • glucocorticoid
  • Alzheimer's
  • oestrogen
  • Huntington's

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