Estrogen modulation of cortical spreading depression.
Estrogen modulation of cortical spreading depression.
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DOI：
10.1186/s10194-023-01598-x
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发表时间：
2023-05-26
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影响因子：
--
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中科院分区：
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皮层扩张性抑制（CSD）是一种短暂的神经元和胶质去极化，在大脑皮层缓慢传播，被认为是偏头痛先兆和头痛诱因的电生理事件。女性偏头痛的发病率是男性的三倍，这与女性荷尔蒙的循环有关。对许多女性来说，高雌激素水平或雌激素消退可能是偏头痛的诱因。因此，我们的目的是研究性别、性腺切除术、女性激素的补充和停药是否会影响CSD的易感性。为了确定CSD的易感性，我们记录了在完整或去性腺的雌性和雄性大鼠中，在没有或通过每日腹腔注射补充雌二醇或黄体酮的情况下，局部使用KCl 2小时引发CSD的频率。在一个单独的队列中研究了雌激素或黄体酮治疗后的停药。为了确定潜在的机制，我们使用放射自显影技术研究了谷氨酸和GABAA受体的结合。完整雌性大鼠的CSD频率高于完整雄性大鼠和去卵巢大鼠。我们没有发现完整雌性在发情周期的不同阶段CSD频率的变化。连续三周每日注射雌激素对CSD频率没有影响。然而，治疗两周后停用雌激素一周，与载体组相比，性腺切除术女性的CSD频率显著增加。同样的雌激素治疗和停药方案在性腺切除术的男性中无效。与雌激素相比，连续三周每天注射黄体酮会增加CSD的易感性，治疗两周后停药一周会部分恢复这种效果。放射自显像未显示雌激素治疗和停药后谷氨酸或GABAA受体结合密度的显著变化。这些数据表明，女性更容易发生CSD，性腺切除术消除了两性二态性。此外，长期每日治疗后的雌激素停药会增加CSD的易感性。这些发现可能对雌激素戒断性偏头痛有影响，尽管后者往往没有先兆。在线版本包含补充材料，可在10.1186/s10194-023-01598-x获得。
Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura and a headache trigger. Migraine is three times more prevalent in women than men, linked to circulating female hormones. High estrogen levels or estrogen withdrawal may be a migraine trigger for many women. We, therefore, aimed to examine whether sex, gonadectomy, and female hormone supplementation and withdrawal affect the susceptibility to CSD. To determine CSD susceptibility, we recorded the frequency of CSDs triggered during 2-h topical KCl application in intact or gonadectomized female and male rats, without or with estradiol or progesterone supplementation via daily intraperitoneal injections. Estrogen or progesterone treatment followed by withdrawal was studied in a separate cohort. To take the first step towards identifying potential mechanisms, we studied glutamate and GABAA receptor binding using autoradiography. The CSD frequency in intact female rats was higher than intact male and ovariectomized rats. We did not detect a change in CSD frequency during different stages of the estrous cycle in intact females. Daily estrogen injections for three weeks did not change CSD frequency. However, one-week estrogen withdrawal after two weeks of treatment significantly increased CSD frequency compared with the vehicle group in gonadectomized females. The same protocol of estrogen treatment and withdrawal was ineffective in gonadectomized males. In contrast to estrogen, daily progesterone injections for three weeks elevated CSD susceptibility, and one-week withdrawal after two weeks of treatment partially normalized this effect. Autoradiography did not reveal significant changes in glutamate or GABAA receptor binding density after estrogen treatment and withdrawal. These data suggest that females are more susceptible to CSD, and sexual dimorphism is abrogated by gonadectomy. Moreover, estrogen withdrawal after prolonged daily treatment enhances CSD susceptibility. These findings may have implications for estrogen-withdrawal migraine, although the latter tends to be without aura. The online version contains supplementary material available at 10.1186/s10194-023-01598-x.
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影响因子：
3.5
作者：
Kunkler, PE;Kraig, RP
通讯作者：
Kraig, RP
DOI：
10.1186/1129-2377-14-62
发表时间：
2013-07-23
期刊：
The journal of headache and pain
影响因子：
--
作者：
Costa C;Tozzi A;Rainero I;Cupini LM;Calabresi P;Ayata C;Sarchielli P
通讯作者：
Sarchielli P
影响因子：
4.9
作者：
Ayata, Cenk
通讯作者：
Ayata, Cenk
影响因子：
4.9
作者：
Chauvel, Virginie;Multon, Sylvie;Schoenen, Jean
通讯作者：
Schoenen, Jean
影响因子：
11.2
作者：
Brennan, Kevin C.;Romero Reyes, Marcela;Charles, Andrew C.
通讯作者：
Charles, Andrew C.