Epilepsy Research Laboratory, University of California, San Francisco, California, USA.
Nat Neurosci. 2013 Jun;16(6):692-7. doi: 10.1038/nn.3392. Epub 2013 May 5.
Impaired GABA-mediated neurotransmission has been implicated in many neurologic diseases, including epilepsy, intellectual disability and psychiatric disorders. We found that inhibitory neuron transplantation into the hippocampus of adult mice with confirmed epilepsy at the time of grafting markedly 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 1,500 μm from the injection site, expressed genes and proteins characteristic for interneurons, differentiated into functional inhibitory neurons and received excitatory synaptic input. In contrast with 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 halting seizures and rescuing accompanying deficits in severely epileptic mice.
抑制性神经递质 GABA 介导的神经传递功能障碍与许多神经疾病有关，包括癫痫、智力障碍和精神疾病。我们发现，在移植时患有明确癫痫的成年小鼠海马区移植抑制性神经元，可显著减少脑电图痫性发作的发生，并恢复空间学习、过度活跃和对处理的攻击反应等行为缺陷。在受者大脑中，GABA 祖细胞从注射部位迁移长达 1500μm，表达具有中间神经元特征的基因和蛋白质，分化为功能性抑制性神经元，并接收兴奋性突触输入。与海马体不同，细胞移植到外侧杏仁核可挽救过度活跃的缺陷，但不改变痫性发作活动或其他异常行为。我们的研究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。
