Zhou L, Fester L, Haghshenas S, de Vrese X, von Hacht R, Gloger S, Brandt N, Bader M, Vollmer G, Rune G M
Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Neuroendocrinol. 2014 Jul;26(7):439-47. doi: 10.1111/jne.12162.
During the oestrus cycle, varying spine synapse density correlates positively with varying local synthesis of oestradiol in the hippocampus. In this context, the roles of the oestrogen receptor (ER) subtypes ERα and β are not fully understood. In the present study, we used neonatal hippocampal slice cultures from female rats because these cultures synthesise oestradiol and express both receptor subtypes, and inhibition of oestradiol synthesis in these cultures results in spine synapse loss. Using electron microscopy, we tested the effects on spine synapse density in response to agonists of both ERα and ERβ. Application of agonists to the cultures had no effect. After inhibition of oestradiol synthesis, however, agonists of ERα induced spine synapse formation, whereas ERβ agonists led to a reduction in spine synapse density in the CA1 region of these cultures. Consistently, up-regulation of ERβ in the hippocampus of adult female aromatase-deficient mice is paralleled by hippocampus-specific spine synapse loss in this mutant. Finally, we found an increase in spine synapses in the adult female ERβ knockout mouse, but no effect in the adult female ERα knockout mouse. Our data suggest antagonistic roles of ERβ and ERα in spine synapse formation in the female hippocampus, which may contribute to oestrus cyclicity of spine synapse density in the hippocampus.
在发情周期中，海马体中不同的脊柱突触密度与雌二醇的局部合成变化呈正相关。在此背景下，雌激素受体（ER）亚型ERα和ERβ的作用尚未完全明确。在本研究中，我们使用了来自雌性大鼠的新生海马切片培养物，因为这些培养物能合成雌二醇并表达两种受体亚型，并且抑制这些培养物中的雌二醇合成会导致脊柱突触丧失。我们使用电子显微镜测试了ERα和ERβ激动剂对脊柱突触密度的影响。向培养物中施加激动剂没有效果。然而，在抑制雌二醇合成后，ERα激动剂诱导了脊柱突触形成，而ERβ激动剂导致这些培养物CA1区域的脊柱突触密度降低。同样，成年雌性芳香化酶缺陷小鼠海马体中ERβ的上调与该突变体中特定于海马体的脊柱突触丧失同时出现。最后，我们发现成年雌性ERβ基因敲除小鼠的脊柱突触增加，但成年雌性ERα基因敲除小鼠没有变化。我们的数据表明，ERβ和ERα在雌性海马体的脊柱突触形成中起拮抗作用，这可能有助于海马体中脊柱突触密度的发情周期变化。
