TY - JOUR
T1 - 17 Beta-oestradiol attenuates dexamethasone-induced lethal and sublethal neuronal damage in the striatum and hippocampus
AU - Haynes, LE
AU - Lendon, Corinne
AU - Barber, David
AU - Mitchell, Ian
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
KW - glucocorticoid
KW - Alzheimer's
KW - oestrogen
KW - Huntington's
UR - http://www.scopus.com/inward/record.url?scp=0041353111&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(03)00167-2
DO - 10.1016/S0306-4522(03)00167-2
M3 - Article
C2 - 12895519
VL - 120
SP - 799
EP - 806
JO - Neuroscience
JF - Neuroscience
IS - 3
ER -