Abstract Title

Mechanisms by which estradiol (E2) suppress neuronal cox-2 gene expression

Presenter Name

Winfred Stacey

Abstract

Purpose:

Data from culture and animal models indicate that 17β-estradiol (E2) deprivation increases susceptibility to neurodegenerative and neuropsychiatric diseases. E2 plays a pivotal role in attenuating inflammatory response in the brain by suppressing expression of proinflammatory genes; however, the molecular mechanisms by which E2 suppress neuronal pro-inflammatory genes are not well established. The pro-inflammatory cyclooxygenase-2 gene (cox-2) is selectively expressed in neuronal populations of the amygdala, hippocampus and cortex. Upregulation of cox-2 expression has been implicated in cascades of deleterious effects that promote neuronal injury and dysfunction. The goal of this study is to elucidate the molecular mechanisms by which E2 suppress cox-2 expression in a neuronal context.

Methods:

To characterize the effect of E2 on cox 2 in a neuronal system, we used the AR-5 immortalized rat neuronal cell line. This cell line was developed by Kasckow et al. from rat embryonic amygdala cells. We first determined that the cell line constitutively expresses COX-2 protein by Western blots and immunocytochemistry and mRNA and hnRNA by RT-qPCR. To assess whether the E2 effect was mediated by ER-alpha (ERα) and/or ER-beta (ERβ), we treated the cells with E2, Diarylpropionitril (DPN), and propyl-pyrazole-triol (PPT). COX-2 mRNA and hnRNA levels were analyzed by RT-qPCR following treatments with the ligands.

Results:

Twenty-four hours of E2 exposure reduces neuronal COX-2 mRNA and hnRNA levels. E2 and DPN treatment led to suppression of COX-2 mRNA and hnRNA after 24hrs. In distinction, PPT had no effect.

Conclusions:

Collectively, the data indicate that E2 suppresses neuronal cox-2 expression through ERβ.

Presentation Type

Poster

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Mechanisms by which estradiol (E2) suppress neuronal cox-2 gene expression

Purpose:

Data from culture and animal models indicate that 17β-estradiol (E2) deprivation increases susceptibility to neurodegenerative and neuropsychiatric diseases. E2 plays a pivotal role in attenuating inflammatory response in the brain by suppressing expression of proinflammatory genes; however, the molecular mechanisms by which E2 suppress neuronal pro-inflammatory genes are not well established. The pro-inflammatory cyclooxygenase-2 gene (cox-2) is selectively expressed in neuronal populations of the amygdala, hippocampus and cortex. Upregulation of cox-2 expression has been implicated in cascades of deleterious effects that promote neuronal injury and dysfunction. The goal of this study is to elucidate the molecular mechanisms by which E2 suppress cox-2 expression in a neuronal context.

Methods:

To characterize the effect of E2 on cox 2 in a neuronal system, we used the AR-5 immortalized rat neuronal cell line. This cell line was developed by Kasckow et al. from rat embryonic amygdala cells. We first determined that the cell line constitutively expresses COX-2 protein by Western blots and immunocytochemistry and mRNA and hnRNA by RT-qPCR. To assess whether the E2 effect was mediated by ER-alpha (ERα) and/or ER-beta (ERβ), we treated the cells with E2, Diarylpropionitril (DPN), and propyl-pyrazole-triol (PPT). COX-2 mRNA and hnRNA levels were analyzed by RT-qPCR following treatments with the ligands.

Results:

Twenty-four hours of E2 exposure reduces neuronal COX-2 mRNA and hnRNA levels. E2 and DPN treatment led to suppression of COX-2 mRNA and hnRNA after 24hrs. In distinction, PPT had no effect.

Conclusions:

Collectively, the data indicate that E2 suppresses neuronal cox-2 expression through ERβ.