Estrogen ameliorates microglial activation by inhibiting the Kir2.1 inward-rectifier K+ channel

Shih Ying Wu, Yun-Wen Chen, Sheng Feng Tsai, Sheng-Nan Wu, Yao Hsiang Shih, Ya Fen Jiang-Shieh, Ting Ting Yang, Yu-Min Kuo

研究成果: Article

15 引文 (Scopus)

摘要

Microglial activation is implicated in the pathogenesis of Parkinson's disease (PD). Although the etiology of PD remains unclear, age and male gender are known PD risk factors. By comparing microglia and dopaminergic (DA) neurons in the substantia nigra (SN) of male and female mice of different ages, we found that the degrees of microglial activation and DA neuron loss increased with age in both genders, but were more pronounced in males, as were peripheral lipopolysaccharide (LPS)-induced microglial activation and DA neuron loss. A bilateral ovariectomy (OVX) eliminated the female-associated protection against age- and LPS-induced microglial activation, which suggests that ovary hormones are involved in gender-specific responses. Treating female mice with 17β-estradiol supplements reduced the age-associated microglial activation in OVX mice. Moreover, pretreating mouse BV2 microglial cells with 17β-estradiol inhibited LPS-induced elevation of Toll-like receptor 4, phosphorylated p38, and TNF-α levels. We then examined the effect of 17β-estradiol on inward-rectifier K+ channel Kir2.1, a known regulator of microglial activation. We found that 17β-estradiol inhibited the Kir2.1 activity of BV2 cells by reducing the probability that the channel would be open. We conclude that age- and inflammation-associated microglial activation is attenuated by ovarian estrogen, because it inhibits Kir2.1.

原文English
文章編號22864
期刊Scientific reports
6
DOIs
出版狀態Published - 2016 三月 10

指紋

Inwardly Rectifying Potassium Channel
Estradiol
Dopaminergic Neurons
Estrogens
Parkinson Disease
Lipopolysaccharides
Toll-Like Receptor 4
Microglia
Ovariectomy
Substantia Nigra
Ovary
Hormones
Inflammation

All Science Journal Classification (ASJC) codes

  • General

引用此文

Wu, Shih Ying ; Chen, Yun-Wen ; Tsai, Sheng Feng ; Wu, Sheng-Nan ; Shih, Yao Hsiang ; Jiang-Shieh, Ya Fen ; Yang, Ting Ting ; Kuo, Yu-Min. / Estrogen ameliorates microglial activation by inhibiting the Kir2.1 inward-rectifier K+ channel. 於: Scientific reports. 2016 ; 卷 6.
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abstract = "Microglial activation is implicated in the pathogenesis of Parkinson's disease (PD). Although the etiology of PD remains unclear, age and male gender are known PD risk factors. By comparing microglia and dopaminergic (DA) neurons in the substantia nigra (SN) of male and female mice of different ages, we found that the degrees of microglial activation and DA neuron loss increased with age in both genders, but were more pronounced in males, as were peripheral lipopolysaccharide (LPS)-induced microglial activation and DA neuron loss. A bilateral ovariectomy (OVX) eliminated the female-associated protection against age- and LPS-induced microglial activation, which suggests that ovary hormones are involved in gender-specific responses. Treating female mice with 17β-estradiol supplements reduced the age-associated microglial activation in OVX mice. Moreover, pretreating mouse BV2 microglial cells with 17β-estradiol inhibited LPS-induced elevation of Toll-like receptor 4, phosphorylated p38, and TNF-α levels. We then examined the effect of 17β-estradiol on inward-rectifier K+ channel Kir2.1, a known regulator of microglial activation. We found that 17β-estradiol inhibited the Kir2.1 activity of BV2 cells by reducing the probability that the channel would be open. We conclude that age- and inflammation-associated microglial activation is attenuated by ovarian estrogen, because it inhibits Kir2.1.",
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Estrogen ameliorates microglial activation by inhibiting the Kir2.1 inward-rectifier K+ channel. / Wu, Shih Ying; Chen, Yun-Wen; Tsai, Sheng Feng; Wu, Sheng-Nan; Shih, Yao Hsiang; Jiang-Shieh, Ya Fen; Yang, Ting Ting; Kuo, Yu-Min.

於: Scientific reports, 卷 6, 22864, 10.03.2016.

研究成果: Article

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