Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice
Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice
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DOI：
10.1073/pnas.0900141106
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发表时间：
2009-09-08
影响因子：
11.1
通讯作者：
Alvarez-Buylla, Arturo
中科院分区：
文献类型：
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作者：
Baraban, Scott C.;Southwell, Derek G.;Alvarez-Buylla, Arturo
癫痫是一种以大脑活动异常为特征的疾病，是一种致残和潜在威胁生命的疾病，占世界人口的近1%。不幸的是，使用可用的抗癫痫药物调节大脑兴奋性可能具有严重的副作用，特别是在发育中的大脑中，并且一些患者只能通过手术切除包含癫痫灶的大脑区域来改善。在这里，我们表明，从胚胎内侧神经节隆起（MGE）的前体细胞到出生后早期的新皮质的双侧移植在宿主脑中产生成熟的GABA能中间神经元。在接受MGE细胞移植的小鼠中，GABA介导的对宿主脑锥体神经元的突触和突触外抑制显著增加。在缺乏Shaker样钾通道（一种在人类癫痫中发生突变的基因）的癫痫小鼠中进行双侧MGE细胞移植，导致自发性电图癫痫发作的持续时间和频率显著减少。我们的研究结果表明，MGE衍生的中间神经元可以用来改善异常的兴奋性，并可能作为一种有效的策略，在癫痫的治疗。
Epilepsy, a disease characterized by abnormal brain activity, is a disabling and potentially life-threatening condition for nearly 1% of the world population. Unfortunately, modulation of brain excitability using available antiepileptic drugs can have serious side effects, especially in the developing brain, and some patients can only be improved by surgical removal of brain regions containing the seizure focus. Here, we show that bilateral transplantation of precursor cells from the embryonic medial ganglionic eminence (MGE) into early postnatal neocortex generates mature GABAergic interneurons in the host brain. In mice receiving MGE cell grafts, GABA-mediated synaptic and extrasynaptic inhibition onto host brain pyramidal neurons is significantly increased. Bilateral MGE cell grafts in epileptic mice lacking a Shaker-like potassium channel (a gene mutated in one form of human epilepsy) resulted in significant reductions in the duration and frequency of spontaneous electrographic seizures. Our findings suggest that MGE-derived interneurons could be used to ameliorate abnormal excitability and possibly act as an effective strategy in the treatment of epilepsy.