title: 17 Beta-oestradiol attenuates dexamethasone-induced lethal and sublethal neuronal damage in the striatum and hippocampus.
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.
authors.affiliation: School of Biomedical Sciences, The Medical School, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. linda.haynes@nottingham.ac.uk
authors.forename: L E
authors.initials: LE
authors.lastname: Haynes
authors.forename: C L
authors.initials: CL
authors.lastname: Lendon
authors.forename: D J
authors.initials: DJ
authors.lastname: Barber
authors.forename: I J
authors.initials: IJ
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005938:Glucocorticoids; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006652:Histological Techniques; D008297:Male; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D005938:Glucocorticoids; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D013629:Tamoxifen; D004958:Estradiol; D003907:Dexamethasone