Female mice lacking ERβ display excitatory/inhibitory synaptic imbalance to drive the pathogenesis of temporal lobe epilepsy.
Female mice lacking ERβ display excitatory/inhibitory synaptic imbalance to drive the pathogenesis of temporal lobe epilepsy.
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缺乏 ERβ 的雌性小鼠表现出兴奋性/抑制性突触失衡，以驱动颞叶癫痫的发病机制。
作者：
Wang Z;Xie R;Yang X;Yin H;Li X;Liu T;Ma Y;Gao J;Zang Z;Ruan R;Li Y;Huang K;Chen Q;Shen K;Lv S;Zhang C;Yang H;Warner M;Gustafsson JA;Liu S;Fan X
癫痫是一种以自发性反复发作为特征的高度流行且药物难治性神经系统疾病。雌激素被确定为促惊厥剂，并降低女性癫痫发作阈值。雌激素受体β（ERβ）介导了癫痫的神经保护作用，但其机制尚不清楚。目的：探讨雌激素受体β（ERβ）在女性颞叶癫痫（TLE）发病中的作用。研究方法：采用免疫组化、免疫荧光、Western印迹、高尔基体染色、1H MRS和全细胞膜片钳技术，观察雌性TLE患者和卵巢切除（OVX）慢性癫痫小鼠海马ERβ表达、病理改变和突触兴奋/抑制（E/I）平衡。记录脑电图（EEG）记录以评估OVX WT和ERβ-/-小鼠的癫痫易感性。并通过高通量RNA测序技术筛选差异表达基因（DEG），以阐明ERβ调节癫痫易感性的可能机制。结果：雌性TLE患者和OVX慢性癫痫小鼠脑内ERβ表达降低。ERβ缺失可增加OVX致痫小鼠的癫痫易感性，并加剧海马CA 1区突触E/I失衡。与这些观察结果一致，RNA序列数据进一步鉴定了谷氨酰胺连接酶（GLUL）作为参与调节CA 1中突触E/I的ERβ的靶标。雌激素受体β激动剂WAY-200070可明显抑制KA慢性致痫模型的癫痫表型和GLUL表达。结论：我们的数据为女性TLE的发病机制提供了新的见解，并表明ERβ为女性TLE患者提供了新的治疗策略。
Epilepsy is a highly prevalent and drug-refractory neurological disorder characterized by spontaneous recurrent seizures. Estrogen is identified to be proconvulsant and lowers the seizure threshold of female epilepsy. Estrogen receptor β (ERβ) has been proposed to mediate neuroprotection in epilepsy, although the underlying mechanism remains unknown. Rationale: In this study, we investigated the role of ERβ in the epileptogenesis of female temporal lobe epilepsy (TLE). Methods: Immunohistochemistry, immunofluorescence, western blots, Golgi staining, 1H MRS and whole-cell patch-clamp were used to evaluate ERβ expression, pathological changes, and synaptic excitation /inhibition (E/I) balance in female TLE patients and ovariectomized (OVX) chronic epileptic mice. Electroencephalogram (EEG) recordings were recorded to evaluate the epileptic susceptibility in OVX WT and ERβ-/- mice. And high-throughput RNA-sequence was performed to identify differential expression genes (DEGs) which can elucidate the potential mechanism of ERβ regulating the seizure susceptibility. Results: ERβ expression was decreased in the brains of female TLE patients and OVX chronic epileptic mice. ERβ deletion enhanced seizure susceptibility and exacerbated the imbalance of synaptic E/I in hippocampal CA1 area of OVX epileptic mice. In line with these observations, RNA-sequence data further identified glutamine ligase (GLUL) as the target of ERβ involved in regulating synaptic E/I in CA1. Furthermore, ERβ agonist WAY-200070 markedly suppressed epileptic phenotypes and normalized GLUL expression in CA1 region of kainic acid (KA) induced OVX chronic epileptic model. Conclusions: Our data provide novel insight into the pathogenesis of female TLE, and indicate ERβ provides a new therapeutic strategy for female TLE patients.
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影响因子：
4.4
作者：
Eid, Tore;Behar, Kevin;Dhaher, Ronnie;Bumanglag, Argyle V.;Lee, Tih-Shih W.
通讯作者：
Lee, Tih-Shih W.
DOI：
10.1523/jneurosci.3191-12.2013
发表时间：
2013-01-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Holth JK;Bomben VC;Reed JG;Inoue T;Younkin L;Younkin SG;Pautler RG;Botas J;Noebels JL
通讯作者：
Noebels JL
影响因子：
56.9
作者：
Bernard, C;Anderson, A;Johnston, D
通讯作者：
Johnston, D
影响因子：
21.1
作者：
Brodie MJ;Besag F;Ettinger AB;Mula M;Gobbi G;Comai S;Aldenkamp AP;Steinhoff BJ
通讯作者：
Steinhoff BJ
影响因子：
82.9
作者：
Maroso, Mattia;Balosso, Silvia;Vezzani, Annamaria
通讯作者：
Vezzani, Annamaria