Estrogen-dependent effects of 5-hydroxytryptophan on cortical spreading depression in rat: Modelling the serotonin-ovarian hormone interaction in migraine aura
Estrogen-dependent effects of 5-hydroxytryptophan on cortical spreading depression in rat: Modelling the serotonin-ovarian hormone interaction in migraine aura
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DOI：
10.1177/0333102417690891
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发表时间：
2018-03-01
期刊：
影响因子：
4.9
通讯作者：
Schoenen, Jean
中科院分区：
文献类型：
--
作者：
Chauvel, Virginie;Multon, Sylvie;Schoenen, Jean
背景：皮质扩散性抑制（CSD）可能是偏头痛先兆的罪魁祸首。偏头痛是性二态性的，被认为是一种“低5-HT”状态。我们试图在偏头痛先兆模型中解释5-羟色胺、卵巢激素和皮质兴奋性之间的相互关系。方法：在成年雄性（n = 16）和雌性（n = 64）大鼠腹腔内（i. p.）注射5-羟色氨酸（5-HTP）或NaCl。65卵巢切除的女性与雌二醇（E2）或胆固醇（Chol）填充胶囊治疗。结果：5-HTP对雄性无影响，但降低了发情期雌性的CSD频率，在顶枕区（-3.5CSD/h，p < 0.001）和额叶区（-2.5CSD/h，p = 0.014）有显著性差异。在卵巢切除的大鼠中，在两个记录部位的E2处理期间CSD敏感性增加（+5CSD/h，p = 0.001和+3CSD/h，p < 0.01），但在E2撤除后迅速降低（-4.7CSD/h，p < 0.001和-1.7CSD/h，p = 0.094）。5-HTP的CSD抑制作用仅在E2处理的大鼠中显著（-3.4CSD/h，p = 0.006和-1.8CSD/h，p = 0.029）。无论是动情周期阶段，也没有E2或5-HTP治疗显着修改CSD的传播velocity.Conclusion：5-HTP降低CSD发生在卵巢激素的存在下，这表明其潜在的疗效在偏头痛与先兆预防女性。E2水平升高会增加CSD的易感性，而雌激素戒断会降低CSD。从转化的角度来看，这些发现可以解释为什么偏头痛先兆可以在怀孕期间出现，以及为什么与月经有关的偏头痛发作很少与先兆有关。
Background: Cortical spreading depression (CSD) is the likely culprit of the migraine aura. Migraine is sexually dimorphic and thought to be a "low 5-HT'' condition. We sought to decipher the interrelation between serotonin, ovarian hormones and cortical excitability in a model of migraine aura.Methods: Occipital KCl-induced CSDs were recorded for one hour at parieto-occipital and frontal levels in adult male (n = 16) and female rats (n = 64) one hour after intraperitoneal (i.p.) injection of 5-hydroxytryptophan (5-HTP) or NaCl. Sixty-five oophorectomized females were treated with estradiol-(E2) or cholesterol-(Chol) filled capsules. Two weeks later we recorded CSDs after 5-HTP/NaCl injections before or 20 hours after capsule removal.Results: 5-HTP had no effect in males, but decreased CSD frequency in cycling females, significantly so during estrus, at parieto-occipital (-3.5CSD/h, p < 0.001) and frontal levels (-2.5CSD/h, p = 0.014). In oophorectomized rats, CSD susceptibility increased during E2 treatment at both recording sites (+5CSD/h, p = 0.001 and +3CSD/h, p < 0.01), but decreased promptly after E2 withdrawal (-4.7CSD/h, p < 0.001 and -1.7CSD/h, p = 0.094). The CSD inhibitory effect of 5-HTP was significant only in E2-treated rats (-3.4CSD/h, p = 0.006 and -1.8CSD/h, p = 0.029). Neither the estrous cycle phase, nor E2 or 5-HTP treatments significantly modified CSD propagation velocity.Conclusion: 5-HTP decreases CSD occurrence in the presence of ovarian hormones, suggesting its potential efficacy in migraine with aura prophylaxis in females. Elevated E2 levels increase CSD susceptibility, while estrogen withdrawal decreases CSD. In a translational perspective, these findings may explain why migraine auras can appear during pregnancy and why menstrual-related migraine attacks are rarely associated with an aura.