hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice.
hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice.
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DOI：
10.1016/j.stem.2014.10.006
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发表时间：
2014-11-06
期刊：
影响因子：
23.9
通讯作者：
Chung, Sangmi
中科院分区：
文献类型：
--
作者：
Cunningham, Miles;Cho, Jun-Hyeong;Leung, Amanda;Savvidis, George;Ahn, Sandra;Moon, Minho;Lee, Paula K. J.;Han, Jason J.;Azimi, Nima;Kim, Kwang-Soo;Bolshakov, Vadim Y.;Chung, Sangmi
癫痫发作障碍使全世界超过65，000，000人衰弱，其中颞叶癫痫（TLE）是最常见的形式。先前的研究表明，GABA释放细胞的移植导致癫痫小鼠癫痫发作的抑制。已经报道了从人PSC衍生中间神经元，指出可以增强抑制性驱动和恢复宿主电路的质量受控的人细胞来源的临床转化。在这项研究中，我们证明了人PSC衍生的成熟GABA能中间神经元（mGIN）广泛迁移并整合到癫痫小鼠大脑功能障碍的电路中。使用光遗传学方法，我们发现移植的mGIN在宿主海马神经元中产生抑制性突触后反应。重要的是，即使在获得完全的电生理成熟之前，移植的神经元也能够抑制癫痫发作并改善行为异常，如认知缺陷，攻击性和多动性。这些结果为人PSC衍生的mGIN用于癫痫的恢复性细胞疗法的潜力提供了支持。
Seizure disorders debilitate more than 65,000,000 people worldwide, with temporal lobe epilepsy (TLE) being the most common form. Previous studies have shown that transplantation of GABA-releasing cells results in suppression of seizures in epileptic mice. Derivation of interneurons from human PSC has been reported, pointing to clinical translation of quality-controlled human cell sources that can enhance inhibitory drive and restore host circuitry. In this study, we demonstrate that human PSC-derived maturing GABAergic interneurons (mGIN) migrate extensively and integrate into dysfunctional circuitry of the epileptic mouse brain. Using optogenetic approaches, we find that grafted mGINs generate inhibitory postsynaptic responses in host hippocampal neurons. Importantly, even before acquiring full electrophysiological maturation, grafted neurons were capable of suppressing seizures and ameliorating behavioral abnormalities such as cognitive deficits, aggressiveness and hyperactivity. These results provide support for the potential of human PSC-derived mGIN for restorative cell therapy for epilepsy.
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影响因子：
14.5
作者：
Marco, P;Sola, RG;DeFelipe, J
通讯作者：
DeFelipe, J
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：
5.3
作者：
Hattiangady, Bharathi;Rao, Muddanna S.;Shetty, Ashok K.
通讯作者：
Shetty, Ashok K.
影响因子：
5.3
作者：
Mueller, Christine J.;Groeticke, Ina;Loescher, Wolfgang
通讯作者：
Loescher, Wolfgang
DOI：
10.1523/jneurosci.2683-11.2012
发表时间：
2012-01-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Maisano X;Litvina E;Tagliatela S;Aaron GB;Grabel LB;Naegele JR
通讯作者：
Naegele JR