Nanomolar dose of bisphenol A rapidly modulates spinogenesis in adult hippocampal neurons
Nanomolar dose of bisphenol A rapidly modulates spinogenesis in adult hippocampal neurons
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DOI：
10.1016/j.mce.2012.01.008
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发表时间：
2012-04
影响因子：
4.1
通讯作者：
Nobuaki Tanabe;Hinako Yoshino;T. Kimoto;Y. Hojo;M. Ogiue‐Ikeda;Y. Shimohigashi;S. Kawato
中科院分区：
文献类型：
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作者：
Nobuaki Tanabe;Hinako Yoshino;T. Kimoto;Y. Hojo;M. Ogiue‐Ikeda;Y. Shimohigashi;S. Kawato
我们证明了10 nM双酚A（BPA）对成年大鼠海马脑片棘突形成的快速影响。通过对切片中注射荧光黄的CA 1神经元成像来分析棘的密度。不仅对脊柱的总密度进行了定量分析，而且对脊柱的头部直径分布也进行了定量分析。BPA在2 h内显著促进了棘状突起的发生。特别是中头棘（头直径为0.4-0.5μm）的密度显著增加。雌激素相关受体γ（ERRγ）和雌激素受体（ERα/ERβ）的拮抗剂羟基他莫昔芬（Hydroxytamoxifen）可阻断BPA引起的棘密度增加。而ERα/ERβ拮抗剂ICI 182，780不能抑制BPA的作用。因此，ERRγ可能是BPA的一个高亲和力受体，参与调控脊髓的发生。MAP激酶抑制剂PD 98059和NMDA受体阻断剂MK-801也能抑制BPA诱导的脊髓生成增强。BPA处理2小时后再冲洗2小时，可消除BPA诱导的棘生成增强作用，表明BPA的作用是可逆的。ERRγ定位于突触和主要神经元胞体。突触上的ERRγ可能有助于观察到的快速效应。通过质谱分析确定海马切片中BPA的水平。
We demonstrated the rapid effects of 10nM bisphenol A (BPA) on the spinogenesis of adult rat hippocampal slices. The density of spines was analyzed by imaging Lucifer Yellow-injected CA1 neurons in slices. Not only the total spine density but also the head diameter distribution of spine was quantitatively analyzed. Spinogenesis was significantly enhanced by BPA within 2h. In particular, the density of middle-head spine (with head diameter of 0.4–0.5μm) was significantly increased. Hydroxytamoxifen, an antagonist of both estrogen-related receptor gamma (ERRγ) and estrogen receptors (ERα/ERβ), blocked the BPA-induced enhancement of the spine density. However, ICI 182,780, an antagonist of ERα/ERβ, did not suppress the BPA effects. Therefore, ERRγ is deduced to be a high affinity receptor of BPA, responsible for modulation of spinogenesis. The BPA-induced enhancement of spinogenesis was also suppressed by MAP kinase inhibitor, PD98059, and the blocker of NMDA receptors, MK-801. Washout of BPA for additional 2h after 2h BPA treatment abolished the BPA-induced enhancement of spinogenesis, suggesting that the BPA effect was reversible. ERRγ was localized at synapses as well as cell bodies of principal neurons. ERRγ at synapses may contribute to the observed rapid effect. The level of BPA in the hippocampal slices was determined by mass-spectrometric analysis.