title: Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus.
abstract: 17β-estradiol (E2) has been implicated to play a critical role in neuroprotection, synaptic plasticity, and cognitive function. Classically, the role of gonadal-derived E2 in these events is well established, but the role of brain-derived E2 is less clear. To address this issue, we investigated the expression, localization, and modulation of aromatase and local E2 levels in the hippocampus following global cerebral ischemia (GCI) in adult ovariectomized rats. Immunohistochemistry (IHC) revealed that the hippocampal regions CA1, CA3 and dentate gyrus (DG) exhibited high levels of immunoreactive aromatase staining, with aromatase being co-localized primarily in neurons in non-ischemic animals. Following GCI, aromatase became highly expressed in GFAP-positive astrocytes in the hippocampal CA1 region at 2-3 days post GCI reperfusion. An ELISA for E2 and IHC for E2 confirmed the GCI-induced elevation of local E2 in the CA1 region and that the increase in local E2 occurred in astrocytes. Furthermore, central administration of aromatase antisense (AS) oligonucleotides, but not missense (MS) oligonucleotides, blocked the increase in aromatase and local E2 in astrocytes after GCI, and resulted in a significant increase in GCI-induced hippocampal CA1 region neuronal cell death and neuroinflammation. As a whole, these results suggest that brain-derived E2 exerts important neuroprotective and anti-inflammatory actions in the hippocampal CA1 region following GCI.
authors: Institute of Molecular Medicine and Genetics, Medical College of Georgia at Georgia Regents University, Augusta, GA 30912, USA. Electronic address: qzhang@gru.edu.
authors: Quan-Guang
authors: QG
authors: Zhang
authors: Institute of Molecular Medicine and Genetics, Medical College of Georgia at Georgia Regents University, Augusta, GA 30912, USA; Neurobiology Institute of Medical Research Centre, Hebei United University, Tangshan, Hebei 063000, PR China.
authors: Ruimin
authors: R
authors: Wang
authors: Institute of Molecular Medicine and Genetics, Medical College of Georgia at Georgia Regents University, Augusta, GA 30912, USA; Neurobiology Institute of Medical Research Centre, Hebei United University, Tangshan, Hebei 063000, PR China.
authors: Hui
authors: H
authors: Tang
authors: Institute of Molecular Medicine and Genetics, Medical College of Georgia at Georgia Regents University, Augusta, GA 30912, USA.
authors: Yan
authors: Y
authors: Dong
authors: Institute of Molecular Medicine and Genetics, Medical College of Georgia at Georgia Regents University, Augusta, GA 30912, USA.
authors: Alice
authors: A
authors: Chan
authors: Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
authors: Gangadhara Reddy
authors: GR
authors: Sareddy
authors: Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
authors: Ratna K
authors: RK
authors: Vadlamudi
authors: Institute of Molecular Medicine and Genetics, Medical College of Georgia at Georgia Regents University, Augusta, GA 30912, USA. Electronic address: dbrann@gru.edu.
authors: Darrell W
authors: DW
authors: Brann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D018891:Dentate Gyrus / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D004967:Estrogens; D018696:Neuroprotective Agents; D004958:Estradiol; D001141:Aromatase
keywords: Aromatase; Brain; Estrogen; Hippocampus; Neuroprotection