GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior.
GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior.
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DOI：
10.1038/nn.3392
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发表时间：
2013-06
影响因子：
25
通讯作者：
Baraban, Scott C.
中科院分区：
文献类型：
--
作者：
Hunt, Robert F.;Girskis, Kelly M.;Rubenstein, John L.;Alvarez-Buylla, Arturo;Baraban, Scott C.
GABA介导的神经传递受损与许多神经系统疾病有关，包括癫痫、智能障碍和精神障碍。在此，我们报告了在移植时将抑制性神经元移植到成年癫痫小鼠的海马区，显著减少了脑电惊厥的发生，并恢复了空间学习、多动和对处理的攻击性反应的行为缺陷。在受体脑中，γ-氨基丁酸前体细胞从注射部位迁移至1500μm，表达中间神经元特有的基因和蛋白，分化为功能性抑制性神经元，并接受兴奋性突触输入。与海马体不同，杏仁核基底外侧的细胞移植可以挽救多动缺陷，但不会改变癫痫发作或其他异常行为。我们的结果强调了中间神经元在癫痫中的关键作用，并表明中间神经元细胞移植是阻止癫痫发作和挽救严重癫痫小鼠伴随缺陷的有效方法。
Impaired GABA–mediated neurotransmission has been implicated in many neurologic diseases including epilepsy, intellectual disability, and psychiatric disorders. Here we report that inhibitory neuron transplantation into the hippocampus of adult mice with confirmed epilepsy at the time of grafting dramatically reduced the occurrence of electrographic seizures and restored behavioral deficits in spatial learning, hyperactivity, and the aggressive response to handling. In the recipient brain, GABA progenitors migrated up to 1500 μm from the injection site, expressed genes and proteins characteristic for interneurons, differentiated into functional inhibitory neurons, and received excitatory synaptic input. In contrast to hippocampus, cell grafts into basolateral amygdala rescued the hyperactivity deficit but did not alter seizure activity or other abnormal behaviors. Our results highlight a critical role for interneurons in epilepsy and suggest that interneuron cell transplantation is a powerful approach to halt seizures and rescue accompanying deficits in severely epileptic mice.
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影响因子：
5.3
作者：
Raber, J;Bongers, G;Mucke, L
通讯作者：
Mucke, L
DOI：
10.1073/pnas.0900141106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Baraban, Scott C.;Southwell, Derek G.;Alvarez-Buylla, Arturo
通讯作者：
Alvarez-Buylla, Arturo
影响因子：
2.6
作者：
Hadjantonakis, AK;Gertsenstein, M;Nagy, A
通讯作者：
Nagy, A
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
25
作者：
Hirsch, JC;Agassandian, C;Bernard, C
通讯作者：
Bernard, C