Neurosteroid replacement therapy for catamenial epilepsy, postpartum depression and neuroendocrine disorders in women.
Neurosteroid replacement therapy for catamenial epilepsy, postpartum depression and neuroendocrine disorders in women.
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DOI：
10.1111/jne.13028
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发表时间：
2022-03
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
神经类固醇参与了许多女性神经内分泌疾病的病理生理学。本文介绍了神经类固醇药理学的最新进展，并强调了神经类固醇替代疗法对神经内分泌疾病（如月经期癫痫、产后抑郁症（PPD）和经前脑部疾病）治疗的益处。神经类固醇是神经元兴奋性的内源性调节剂。多种神经类固醇存在于大脑中，包括别孕烯醇酮（AP）、THDOC和雄甾烷酮。神经类固醇与脑中的突触和突触外GABA-A受体相互作用。AP和相关的神经类固醇是GABA-A受体的正变构调节剂，是强效的抗惊厥剂、抗焦虑剂、抗应激剂和神经保护剂。在月经性癫痫中，癫痫发作通常集中在女性的特定月经期。突触外受体的神经类固醇戒断相关可塑性已被证明在月经性癫痫发作、焦虑和其他情绪障碍中起关键作用。基于我们二十年的广泛研究，我们提出并支持神经类固醇替代疗法（NRT）作为治疗以神经类固醇缺乏为标志的疾病的合理策略，如月经性癫痫和其他相关的卵巢或月经紊乱。2019年，AP（更名为Brexanolone）被批准用于治疗PPD。多种合成神经类固醇正在进行癫痫、抑郁和其他脑部疾病的临床试验。我们对神经类固醇的理解的最新进展已经进入了药物发现的新时代，这为治疗复杂的大脑疾病提供了很高的治疗潜力。神经类固醇在月经性癫痫和许多神经内分泌疾病中起着关键作用。神经类固醇缺乏导致紧张性抑制减少和癫痫发作、焦虑或烦躁行为增强。GABA-A受体丰度或分布的变化影响神经类固醇反应。神经类固醇替代疗法（NRT）是CE，PPD和经前情绪障碍的独特策略。各种合成神经类固醇正在进行神经内分泌疾病的临床试验。
Neurosteroids are involved in the pathophysiology of many neuroendocrine disorders in women. This article describes recent advancements in pharmacology of neurosteroids and emphasizes the benefits of neurosteroid replacement therapy for the management of neuroendocrine disorders such as catamenial epilepsy, postpartum depression (PPD), and premenstrual brain conditions. Neurosteroids are endogenous modulators of neuronal excitability. A variety of neurosteroids are present in the brain including allopregnanolone (AP), THDOC, and androstanediol. Neurosteroids interact with synaptic and extrasynaptic GABA-A receptors in the brain. AP and related neurosteroids, which are positive allosteric modulators of GABA-A receptors, are powerful anticonvulsants, anxiolytic, antistress, and neuroprotectant agents. In catamenial epilepsy, seizures are most often clustered around a specific menstrual period in women. Neurosteroid withdrawal-linked plasticity in extrasynaptic receptors has been shown to play a key role in catamenial seizures, anxiety, and other mood disorders. Based on our extensive research spanning two decades, we have proposed and championed neurosteroid replacement therapy (NRT) as a rational strategy for treating disorders marked by neurosteroid-deficiency, such as catamenial epilepsy and other related ovarian or menstrual disorders. In 2019, AP (renamed as brexanolone) was approved for treating PPD. A variety of synthetic neurosteroids are in clinical trials for epilepsy, depression, and other brain disorders. Recent advancements in our understanding of neurosteroids have entered a new era of drug discovery, one that offers a high therapeutic potential for treating complex brain disorders. Neurosteroids play a critical role in catamenial epilepsy and many neuroendocrine disorders. Neurosteroid deficiency leads to reduced tonic inhibition and enhanced seizures, anxiety, or dysphoric behavior. Changes in the abundance or distribution of GABA-A receptors affect the neurosteroid response. Neurosteroid replacement therapy (NRT) is a unique strategy for CE, PPD, and premenstrual mood disorders. A variety of synthetic neurosteroids are in clinical trials for neuroendocrine conditions.
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影响因子：
5.8
作者：
Björn, I;Sundström-Poromaa, IS;Bäckström, T
通讯作者：
Bäckström, T
DOI：
10.1016/0960-0760(90)90490-c
发表时间：
1990-11-20
影响因子：
4.1
作者：
BAULIEU, EE;ROBEL, P
通讯作者：
ROBEL, P
影响因子：
4.8
作者：
Brandon, NJ;Delmas, P;Moss, SJ
通讯作者：
Moss, SJ
影响因子：
4.2
作者：
Caruso, Donatella;Barron, Anna M.;Melcangi, Roberto C.
通讯作者：
Melcangi, Roberto C.
DOI：
10.1124/jpet.117.246660
发表时间：
2018-06-01
影响因子：
3.5
作者：
Chuang, Shu-Hui;Reddy, Doodipala Samba
通讯作者：
Reddy, Doodipala Samba