Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University (Formerly University of Dammam), Dammam 31441, Saudi Arabia.
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New-Delhi, India.
Curr Neuropharmacol. 2019;17(3):214-231. doi: 10.2174/1570159X16666180628164432.
A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injunction of epileptic seizures and epileptogenesis. Estrogen administration in animals reduces neuronal death from seizures by up-regulation of the prosurvival molecule i.e. Bcl-2, anti-oxidant potential and protection of NPY interneurons. Serotonin modulates epileptiform activity in either direction i.e administration of 5-HT agonists or reuptake inhibitors leads to the activation of 5-HT3 and 5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with the destruction of serotonergic terminals leads to expanded neuronal excitability hence abatement of seizure threshold in experimental animal models. Serotonergic neurotransmission is influenced by the organizational activity of steroid hormones in the growing brain and the actuation effects of steroids which come in adulthood. It is further established that ovarian steroids bring induction of dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission. This review features 5-HT1A and 5-HT3 receptors as potential targets for ameliorating seizure-induced neurodegeneration and recurrent hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate cross-talk between estrogenic and serotonergic pathways, and could be well exploited for combinatorial drug therapy against epileptogenesis.
日益增多的文献资料表明，卵巢类固醇激素和中枢 5-羟色胺能系统在癫痫发作和癫痫发生中的融合。在动物中给予雌激素可通过上调生存分子（即 Bcl-2）、抗氧化潜力和保护 NPY 中间神经元来减少癫痫发作引起的神经元死亡。5-羟色胺可调节癫痫样活动的方向，即给予 5-HT 激动剂或再摄取抑制剂会激活 5-HT3 和 5-HT1A 受体，倾向于阻止局灶性和全身性癫痫发作，而脑内 5-HT 的耗竭以及 5-羟色胺能末梢的破坏会导致神经元兴奋性增加，从而降低实验动物模型中的癫痫发作阈值。5-羟色胺能神经传递受生长中大脑中类固醇激素的组织活动和成年后类固醇激素的启动作用的影响。进一步证实，卵巢类固醇激素诱导 5-羟色胺能神经元树突棘的增殖，从而对 5-羟色胺能传递产生深远影响。这篇综述以 5-HT1A 和 5-HT3 受体为潜在靶点，以改善癫痫引起的神经退行性变和复发性过度同步神经元活动。事实上，5-HT3 受体介导了雌激素和 5-羟色胺能途径之间的串扰，并且可以很好地用于针对癫痫发生的组合药物治疗。
