GABA(A) receptors in normal development and seizures: friends or foes?
GABA(A) receptors in normal development and seizures: friends or foes?
复制标题
DOI：
10.2174/157015908783769653
复制
发表时间：
2008-03
影响因子：
5.3
通讯作者：
Galanopoulou AS
中科院分区：
文献类型：
--
作者：
Galanopoulou AS
GABAA受体在大脑中具有与年龄相适应的功能。在早期发育过程中，它们介导兴奋作用，导致钙敏感信号过程的激活，这对大脑的分化很重要。在更成熟的发育阶段和成人中，GABAA受体传递抑制信号。GABAA信号的成熟遵循性别特异性模式，这似乎对大脑的性别分化也很重要。GABAA受体激活的抑制作用已被广泛应用于治疗需要神经元沉默的疾病。例如，靶向GABAA受体的药物是治疗癫痫发作的主要药物。然而，最近的证据表明，在患有癫痫或癫痫持续状态的受试者的大脑中，GABAA受体的生理和功能发生了变化。本文就GABAA受体信号转导和功能调控的生理及发育因素作一综述；这些在经历过癫痫发作的大脑中是如何变化的；癫痫发作和癫痫持续状态的年龄和性别特异性治疗的意义是什么？最后，这些变化对治疗某些形式的难治性癫痫和癫痫持续状态的影响将被讨论。
GABAA receptors have an age-adapted function in the brain. During early development, they mediate excitatory effects resulting in activation of calcium sensitive signaling processes that are important for the differentiation of the brain. In more mature stages of development and in adults, GABAA receptors transmit inhibitory signals. The maturation of GABAA signaling follows sex-specific patterns, which appear to also be important for the sexual differentiation of the brain. The inhibitory effects of GABAA receptor activation have been widely exploited in the treatment of conditions where neuronal silencing is necessary. For instance, drugs that target GABAA receptors are the mainstay of treatment of seizures. Recent evidence suggests however that the physiology and function of GABAA receptors changes in the brain of a subject that has epilepsy or status epilepticus. This review will summarize the physiology of and the developmental factors regulating the signaling and function of GABAA receptors; how these may change in the brain that has experienced prior seizures; what are the implications for the age and sex specific treatment of seizures and status epilepticus. Finally, the implications of these changes for the treatment of certain forms of medically refractory epilepsies and status epilepticus will be discussed.