Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory Neuro-diseases and Multi-morbidity, West China Hospital, Sichuan University, Chengdu, China.
Neuroendocrinology. 2024;114(11):1005-1017. doi: 10.1159/000540523. Epub 2024 Jul 25.
In women of childbearing age with epilepsy, 30% experience the comorbidity of polycystic ovary syndrome (PCOS), which is marked by a higher prevalence of hyperandrogenism. Our recent clinical observations indicate the potential contribution of hyperandrogenism-induced PCOS to epilepsy susceptibility, and this study aimed to unravel the underlying factors that increase the susceptibility of females to epilepsy.
A letrozole-induced PCOS rat model was employed to simulate endogenous hyperandrogenism. The threshold of seizure was assessed through seizure kindling rates using pentetrazol and electroencephalogram recordings. Additionally, the role of androgens in epilepsy was verified through interventions using Diane-35.
This study revealed that letrozole-induced elevated testosterone levels and PCOS-related changes in female rats. PCOS rats, through pentetrazol-kindling, exhibited a reduced seizure threshold compared with controls. Elevated testosterone levels were observed in both the hippocampal and frontal brain tissues, accompanied by changes in circulation. Two weeks of Diane-35 intervention showed a tendency to alleviate these changes, modifying testosterone levels in both the plasma and brain tissue. Western blotting and immunohistochemistry revealed increased expression of GABA-A receptor in the hippocampus and decreased AMPA receptor expression in the frontal cortex, correlating with antiepileptic status in PCOS rats.
This study delves into the impact of elevated androgen levels on seizure threshold, providing crucial insights into the underpinnings of the comorbidity between PCOS and epilepsy. These findings significantly contribute to the evolving field of epilepsy research, emphasizing the imperative consideration of hormonal influences for the development of targeted therapeutic interventions in individuals with epilepsy and PCOS.
在育龄期癫痫女性中，有 30% 患有多囊卵巢综合征（PCOS），其特点是高雄激素血症的发病率更高。我们最近的临床观察表明，高雄激素血症诱导的 PCOS 可能导致癫痫易感性增加，本研究旨在揭示增加女性癫痫易感性的潜在因素。
使用来曲唑诱导的 PCOS 大鼠模型模拟内源性高雄激素血症。通过戊四氮和脑电图记录评估癫痫发作的发作阈值。此外，通过使用 Diane-35 进行干预来验证雄激素在癫痫中的作用。
本研究表明，来曲唑诱导的大鼠睾酮水平升高和 PCOS 相关变化。与对照组相比，PCOS 大鼠通过戊四氮点燃表现出较低的发作阈值。在海马和额叶脑组织中均观察到睾酮水平升高，同时循环中也发生变化。两周的 Diane-35 干预显示出减轻这些变化的趋势，改变了血浆和脑组织中的睾酮水平。Western blot 和免疫组织化学显示海马中 GABA-A 受体表达增加，额叶皮质中 AMPA 受体表达减少，与 PCOS 大鼠的抗癫痫状态相关。
本研究探讨了升高的雄激素水平对发作阈值的影响，为 PCOS 和癫痫共病的基础提供了重要见解。这些发现为癫痫研究领域的发展做出了重要贡献，强调了在癫痫和 PCOS 个体中，考虑激素影响对于开发靶向治疗干预措施的重要性。
