Estrogen receptor beta signaling alters cellular inflammasomes activity after global cerebral ischemia in reproductively senescence female rats

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Abstract

Periodic treatments with estrogen receptor subtype-β (ER-β) agonist reduce post-ischemic hippocampal injury in ovariectomized rats. However, the underlying mechanism of how ER-β agonists protect the brain remains unknown. Global cerebral ischemia activates the innate immune response, and a key component of the innate immune response is the inflammasome. This study tests the hypothesis that ER-β regulates inflammasome activation in the hippocampus, thus reducing ischemic hippocampal damage in reproductively senescent female rats that received periodic ER-β agonist treatments. First, we determined the effect of hippocampal ER-β silencing on the expression of the inflammasome proteins caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β. Silencing of ER-β attenuated 17β-estradiol mediated decrease in caspase 1, ASC, and IL-1β. Next, we tested the hypothesis that periodic ER-β agonist treatment reduces inflammasome activation and ischemic damage in reproductively senescent female rats. Periodic ER-β agonist treatments significantly decreased inflammasome activation and increased post-ischemic live neuronal counts by 32% (p <0.05) as compared to the vehicle-treated, reproductively senescent rats. Current findings demonstrated that ER-β activation regulates inflammasome activation and protects the brain from global ischemic damage in reproductively senescent female rats. Further investigation on the role of a periodic ER-β agonist regimen to reduce the innate immune response in the brain could help reduce the incidence and the impact of global cerebral ischemia in post-menopausal women.

Original languageEnglish (US)
Pages (from-to)492-496
Number of pages5
JournalJournal of Neurochemistry
Volume136
Issue number3
DOIs
StatePublished - Feb 1 2016

Fingerprint

Inflammasomes
Cell signaling
Estrogen Receptor beta
Brain Ischemia
Rats
Estrogens
Estrogen Receptors
Chemical activation
Innate Immunity
Caspase 1
Brain
Interleukin-1
Therapeutics
Estradiol
Hippocampus
Proteins
Apoptosis
Incidence
Wounds and Injuries

Keywords

  • caspase-1
  • cerebral ischemia
  • interleukin 1beta
  • neuroprotection
  • NOD-like receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Estrogen receptor beta signaling alters cellular inflammasomes activity after global cerebral ischemia in reproductively senescence female rats",
abstract = "Periodic treatments with estrogen receptor subtype-β (ER-β) agonist reduce post-ischemic hippocampal injury in ovariectomized rats. However, the underlying mechanism of how ER-β agonists protect the brain remains unknown. Global cerebral ischemia activates the innate immune response, and a key component of the innate immune response is the inflammasome. This study tests the hypothesis that ER-β regulates inflammasome activation in the hippocampus, thus reducing ischemic hippocampal damage in reproductively senescent female rats that received periodic ER-β agonist treatments. First, we determined the effect of hippocampal ER-β silencing on the expression of the inflammasome proteins caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β. Silencing of ER-β attenuated 17β-estradiol mediated decrease in caspase 1, ASC, and IL-1β. Next, we tested the hypothesis that periodic ER-β agonist treatment reduces inflammasome activation and ischemic damage in reproductively senescent female rats. Periodic ER-β agonist treatments significantly decreased inflammasome activation and increased post-ischemic live neuronal counts by 32{\%} (p <0.05) as compared to the vehicle-treated, reproductively senescent rats. Current findings demonstrated that ER-β activation regulates inflammasome activation and protects the brain from global ischemic damage in reproductively senescent female rats. Further investigation on the role of a periodic ER-β agonist regimen to reduce the innate immune response in the brain could help reduce the incidence and the impact of global cerebral ischemia in post-menopausal women.",
keywords = "caspase-1, cerebral ischemia, interleukin 1beta, neuroprotection, NOD-like receptor",
author = "{de Rivero Vaccari}, {Juan Pablo P} and Patel, {Hersila H.} and Brand, {Frank J.} and Miguel Perez-Pinzon and Helen Bramlett and Ami Raval",
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AU - de Rivero Vaccari, Juan Pablo P

AU - Patel, Hersila H.

AU - Brand, Frank J.

AU - Perez-Pinzon, Miguel

AU - Bramlett, Helen

AU - Raval, Ami

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Periodic treatments with estrogen receptor subtype-β (ER-β) agonist reduce post-ischemic hippocampal injury in ovariectomized rats. However, the underlying mechanism of how ER-β agonists protect the brain remains unknown. Global cerebral ischemia activates the innate immune response, and a key component of the innate immune response is the inflammasome. This study tests the hypothesis that ER-β regulates inflammasome activation in the hippocampus, thus reducing ischemic hippocampal damage in reproductively senescent female rats that received periodic ER-β agonist treatments. First, we determined the effect of hippocampal ER-β silencing on the expression of the inflammasome proteins caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β. Silencing of ER-β attenuated 17β-estradiol mediated decrease in caspase 1, ASC, and IL-1β. Next, we tested the hypothesis that periodic ER-β agonist treatment reduces inflammasome activation and ischemic damage in reproductively senescent female rats. Periodic ER-β agonist treatments significantly decreased inflammasome activation and increased post-ischemic live neuronal counts by 32% (p <0.05) as compared to the vehicle-treated, reproductively senescent rats. Current findings demonstrated that ER-β activation regulates inflammasome activation and protects the brain from global ischemic damage in reproductively senescent female rats. Further investigation on the role of a periodic ER-β agonist regimen to reduce the innate immune response in the brain could help reduce the incidence and the impact of global cerebral ischemia in post-menopausal women.

AB - Periodic treatments with estrogen receptor subtype-β (ER-β) agonist reduce post-ischemic hippocampal injury in ovariectomized rats. However, the underlying mechanism of how ER-β agonists protect the brain remains unknown. Global cerebral ischemia activates the innate immune response, and a key component of the innate immune response is the inflammasome. This study tests the hypothesis that ER-β regulates inflammasome activation in the hippocampus, thus reducing ischemic hippocampal damage in reproductively senescent female rats that received periodic ER-β agonist treatments. First, we determined the effect of hippocampal ER-β silencing on the expression of the inflammasome proteins caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin (IL)-1β. Silencing of ER-β attenuated 17β-estradiol mediated decrease in caspase 1, ASC, and IL-1β. Next, we tested the hypothesis that periodic ER-β agonist treatment reduces inflammasome activation and ischemic damage in reproductively senescent female rats. Periodic ER-β agonist treatments significantly decreased inflammasome activation and increased post-ischemic live neuronal counts by 32% (p <0.05) as compared to the vehicle-treated, reproductively senescent rats. Current findings demonstrated that ER-β activation regulates inflammasome activation and protects the brain from global ischemic damage in reproductively senescent female rats. Further investigation on the role of a periodic ER-β agonist regimen to reduce the innate immune response in the brain could help reduce the incidence and the impact of global cerebral ischemia in post-menopausal women.

KW - caspase-1

KW - cerebral ischemia

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KW - NOD-like receptor

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