title: Estrogen receptors alpha mediates postischemic inflammation in chronically estrogen-deprived mice.
abstract: Estrogens are known to exert neuroprotective and immuneomodulatory effects after stroke. However, at present, little is known about the role of estrogens and its receptors in postischemic inflammation after menopause. Here, we provide important in vivo evidence of a distinct shift in microglial phenotypes in the model of postmenopause brain. Using a model-system for live imaging of microglial activation in the context of chronic estrogen- and ERα-deficiency associated with aging, we observed a marked deregulation of the TLR2 signals and/or microglial activation in ovariectomized and/or ERα knockout mice. Further analysis revealed a 5.7-fold increase in IL-6, a 4.7-fold increase in phospho-Stat3 levels suggesting an overactivation of JAK/STAT3 pathway and significantly larger infarction in ERα knockouts chronically deprived of estrogen. Taken together, our results suggest that in the experimental model of menopause and/or aging, ERα mediates innate immune responses and/or microglial activation, and ischemia-induced production of IL-6. Based on our results, we propose that the loss of functional ERα may lead to deregulation of postischemic inflammatory responses and increased vulnerability to ischemic injury in aging female brains.
authors.affiliation: Faculty of Medicine, Department of Psychiatry and Neuroscience, Research Centre of Institut universitaire en santé mentale de Québec, Laval University, Québec, Québec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordeau
authors.affiliation: Faculty of Medicine, Department of Psychiatry and Neuroscience, Research Centre of Institut universitaire en santé mentale de Québec, Laval University, Québec, Québec, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lalancette-Hébert
authors.affiliation: Faculty of Medicine, Department of Psychiatry and Neuroscience, Research Centre of Institut universitaire en santé mentale de Québec, Laval University, Québec, Québec, Canada.
authors.forename: Yuan Cheng
authors.initials: YC
authors.lastname: Weng
authors.affiliation: Faculty of Medicine, Department of Psychiatry and Neuroscience, Research Centre of Institut universitaire en santé mentale de Québec, Laval University, Québec, Québec, Canada. Electronic address: jasna.kriz@fmed.ulaval.ca.
authors.forename: Jasna
authors.initials: J
authors.lastname: Kriz
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000172:deficiency* / Q000502:physiology*; D004967:Estrogens / Q000172:deficiency / Q000502:physiology; D005260:Female; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000378:metabolism; D008593:Menopause; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D023421:Models, Animal; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: Galectin-3; IL-6; Menopause; Microglia; Neruoinflammation; Stroke; TLR2