Estrogen Protects against Global Ischemia-Induced Neuronal Death and Prevents Activation of Apoptotic Signaling Cascades in the Hippocampal CA1
| Autor: | Anne M. Etgen, Agata Calderone, Michael V. L. Bennett, Hidenobu Tanaka, Teresa Jover, R. Suzanne Zukin, Keiji Oguro |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Blotting Western Ischemia Down-Regulation Apoptosis Receptors Nerve Growth Factor AMPA receptor Tropomyosin receptor kinase A Biology Hippocampal formation Hippocampus Receptor Nerve Growth Factor Brain Ischemia Brain ischemia Downregulation and upregulation Internal medicine medicine Animals RNA Messenger Receptors AMPA ARTICLE In Situ Hybridization Neurons Caspase 3 Glutamate Decarboxylase General Neuroscience Dentate gyrus Estrogens medicine.disease Up-Regulation Enzyme Activation Endocrinology nervous system Cytoprotection Estrogen Caspases Gerbillinae Signal Transduction |
| Zdroj: | The Journal of Neuroscience. 22:2115-2124 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.22-06-02115.2002 |
| Popis: | The importance of postmenopausal estrogen replacement therapy in affording protection against the selective and delayed neuronal death associated with cardiac arrest or cardiac surgery in women remains controversial. Here we report that exogenous estrogen at levels that are physiological for hormone replacement in postmenopausal women affords protection against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1 of male gerbils. Global ischemia induced a marked increase in activated caspase-3 in CA1, evident at 6 hr after ischemia. Global ischemia induced a marked upregulation of the proapoptotic neurotrophin receptor p75NTRin CA1, evident at 48 hr. p75NTRexpression was induced primarily in terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling-positive cells, indicating expression in neurons undergoing apoptosis. Global ischemia also induced a marked downregulation of mRNA encoding the AMPA receptor GluR2 subunit in CA1. Caspase-3, p75NTR, and GluR2 were not significantly changed in CA3 and dentate gyrus, indicating that the ischemia-induced changes in gene expression were cell specific. Exogenous estrogen attenuated the ischemia-induced increases in activated caspase-3 and blocked the increase in p75NTRin post-ischemic CA1 neurons but did not prevent ischemia-induced downregulation of GluR2. These findings demonstrate that long-term estrogen at physiological levels ameliorates ischemia-induced hippocampal injury and indicate that estrogen intervenes at the level of apoptotic signaling cascades to prevent onset of death in neurons otherwise “destined to die.” |
| Databáze: | OpenAIRE |
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