Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats
Smoking is a preventable risk factor for stroke and smoking-derived nicotine exacerbates post-ischemic damage via inhibition of estrogen receptor beta (ER-β) signaling in the brain of female rats. ER-β regulates inflammasome activation in the brain. Therefore, we hypothesized that...
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doaj-28225cfcc24c4c1396414c79b221f8ec2020-11-24T23:59:40ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-04-01195133010.3390/ijms19051330ijms19051330Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female RatsNathan D. d’Adesky0Juan Pablo de Rivero Vaccari1Pallab Bhattacharya2Marc Schatz3Miguel A. Perez-Pinzon4Helen M. Bramlett5Ami P. Raval6Cerebral Vascular Disease Research Center, Department of Neurology and Neuroscience Program (D4-5), P.O. Box 016960, University of Miami School of Medicine, Miami, FL 33101, USADepartment of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33136, USACerebral Vascular Disease Research Center, Department of Neurology and Neuroscience Program (D4-5), P.O. Box 016960, University of Miami School of Medicine, Miami, FL 33101, USACerebral Vascular Disease Research Center, Department of Neurology and Neuroscience Program (D4-5), P.O. Box 016960, University of Miami School of Medicine, Miami, FL 33101, USACerebral Vascular Disease Research Center, Department of Neurology and Neuroscience Program (D4-5), P.O. Box 016960, University of Miami School of Medicine, Miami, FL 33101, USADepartment of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33136, USACerebral Vascular Disease Research Center, Department of Neurology and Neuroscience Program (D4-5), P.O. Box 016960, University of Miami School of Medicine, Miami, FL 33101, USASmoking is a preventable risk factor for stroke and smoking-derived nicotine exacerbates post-ischemic damage via inhibition of estrogen receptor beta (ER-β) signaling in the brain of female rats. ER-β regulates inflammasome activation in the brain. Therefore, we hypothesized that chronic nicotine exposure activates the inflammasome in the brain, thus exacerbating ischemic brain damage in female rats. To test this hypothesis, adult female Sprague-Dawley rats (6–7 months old) were exposed to nicotine (4.5 mg/kg/day) or saline for 16 days. Subsequently, brain tissue was collected for immunoblot analysis. In addition, another set of rats underwent transient middle cerebral artery occlusion (tMCAO; 90 min) with or without nicotine exposure. One month after tMCAO, histopathological analysis revealed a significant increase in infarct volume in the nicotine-treated group (64.24 ± 7.3 mm3; mean ± SEM; n = 6) compared to the saline-treated group (37.12 ± 7.37 mm3; n = 7, p < 0.05). Immunoblot analysis indicated that nicotine increased cortical protein levels of caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-inflammatory cytokines interleukin (IL)-1β by 88% (p < 0.05), 48% (p < 0.05) and 149% (p < 0.05), respectively, when compared to the saline-treated group. Next, using an in vitro model of ischemia in organotypic slice cultures, we tested the hypothesis that inhibition of nicotine-induced inflammasome activation improves post-ischemic neuronal survival. Accordingly, slices were exposed to nicotine (100 ng/mL; 14–16 days) or saline, followed by treatment with the inflammasome inhibitor isoliquiritigenin (ILG; 24 h) prior to oxygen-glucose deprivation (OGD; 45 min). Quantification of neuronal death demonstrated that inflammasome inhibition significantly decreased nicotine-induced ischemic neuronal death. Overall, this study shows that chronic nicotine exposure exacerbates ischemic brain damage via activation of the inflammasome in the brain of female rats.http://www.mdpi.com/1422-0067/19/5/1330strokeinflammasomenicotineestrogensmokingwomen’s health |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathan D. d’Adesky Juan Pablo de Rivero Vaccari Pallab Bhattacharya Marc Schatz Miguel A. Perez-Pinzon Helen M. Bramlett Ami P. Raval |
spellingShingle |
Nathan D. d’Adesky Juan Pablo de Rivero Vaccari Pallab Bhattacharya Marc Schatz Miguel A. Perez-Pinzon Helen M. Bramlett Ami P. Raval Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats International Journal of Molecular Sciences stroke inflammasome nicotine estrogen smoking women’s health |
author_facet |
Nathan D. d’Adesky Juan Pablo de Rivero Vaccari Pallab Bhattacharya Marc Schatz Miguel A. Perez-Pinzon Helen M. Bramlett Ami P. Raval |
author_sort |
Nathan D. d’Adesky |
title |
Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats |
title_short |
Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats |
title_full |
Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats |
title_fullStr |
Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats |
title_full_unstemmed |
Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats |
title_sort |
nicotine alters estrogen receptor-beta-regulated inflammasome activity and exacerbates ischemic brain damage in female rats |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-04-01 |
description |
Smoking is a preventable risk factor for stroke and smoking-derived nicotine exacerbates post-ischemic damage via inhibition of estrogen receptor beta (ER-β) signaling in the brain of female rats. ER-β regulates inflammasome activation in the brain. Therefore, we hypothesized that chronic nicotine exposure activates the inflammasome in the brain, thus exacerbating ischemic brain damage in female rats. To test this hypothesis, adult female Sprague-Dawley rats (6–7 months old) were exposed to nicotine (4.5 mg/kg/day) or saline for 16 days. Subsequently, brain tissue was collected for immunoblot analysis. In addition, another set of rats underwent transient middle cerebral artery occlusion (tMCAO; 90 min) with or without nicotine exposure. One month after tMCAO, histopathological analysis revealed a significant increase in infarct volume in the nicotine-treated group (64.24 ± 7.3 mm3; mean ± SEM; n = 6) compared to the saline-treated group (37.12 ± 7.37 mm3; n = 7, p < 0.05). Immunoblot analysis indicated that nicotine increased cortical protein levels of caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-inflammatory cytokines interleukin (IL)-1β by 88% (p < 0.05), 48% (p < 0.05) and 149% (p < 0.05), respectively, when compared to the saline-treated group. Next, using an in vitro model of ischemia in organotypic slice cultures, we tested the hypothesis that inhibition of nicotine-induced inflammasome activation improves post-ischemic neuronal survival. Accordingly, slices were exposed to nicotine (100 ng/mL; 14–16 days) or saline, followed by treatment with the inflammasome inhibitor isoliquiritigenin (ILG; 24 h) prior to oxygen-glucose deprivation (OGD; 45 min). Quantification of neuronal death demonstrated that inflammasome inhibition significantly decreased nicotine-induced ischemic neuronal death. Overall, this study shows that chronic nicotine exposure exacerbates ischemic brain damage via activation of the inflammasome in the brain of female rats. |
topic |
stroke inflammasome nicotine estrogen smoking women’s health |
url |
http://www.mdpi.com/1422-0067/19/5/1330 |
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