Montreal Neurological Institute-Hospital & Department of Neurology and Neurosurgery, 3801 University Street, Montreal, QC H3A 2B4, Canada.
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Università 4, 41121 Modena, Italy.
Int J Mol Sci. 2020 Dec 10;21(24):9391. doi: 10.3390/ijms21249391.
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABA receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80-500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders.
神经甾体是一类化合物，主要在兴奋性神经元和神经胶质细胞中合成，来源于胆固醇转化为孕烯醇酮。研究最多的神经甾体-别孕烯醇酮和别四氢脱氧皮质酮（THDOC）-已知可调节 GABA 受体介导的传递，从而在控制神经元网络兴奋性方面发挥作用。鉴于 GABA 信号在癫痫疾病中的作用，神经甾体对癫痫发作的产生有深远影响，并在慢性癫痫状态的发展中发挥作用（即癫痫发生）。我们在这里回顾了研究表明神经甾体对体外脑片上癫痫样同步的影响，对体内模型中癫痫活动的影响，即在化学惊厥治疗致痫的动物中，以及对癫痫患者的影响。这些研究表明，神经甾体可以调节癫痫发生和病理性网络活动的发生，如发作间期棘波和高频振荡（80-500 Hz）。此外，它们可以延迟内侧颞叶癫痫动物模型中自发性癫痫发作的发作。总的来说，这些证据表明神经甾体代表了治疗局灶性癫痫疾病的新靶点。
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