抑制癫痫时海马神经元损伤的新发现

抑制癫痫时海马神经元损伤的新发现

课题组以往研究发现小肽Tat-GluR6-9c (含有谷氨酸受体6羧基末端的9个氨基酸的融合肽)可以传送到海马神经元。在海人藻酸诱导的癫痫模型中发现谷氨酸受体6-PSD-95-MLK3信号模块在海马CA1区组装。为此，来自中国徐州医学院裴冬生教授所在课题组进行的一项研究将GluR6的羧基末端克隆至腺病毒中，将构建的病毒颗粒注射到大鼠海马CA1区，发现它能抑制GluR6-PSD-95-MLK3信号模块的组装，阻止JNK信号通路的活化，减少了海人藻酸诱导的海马CA1区神经元的死亡，发挥了对神经元的保护作用。研究结果为癫痫的基因治疗提供了一种可能方法。文章发表在《中国神经再生研究（英文版）》杂志2014年12月第23期。

免疫组织化学染色检测显示，注射Ad-GluR6c能显著减轻海人藻酸诱导的神经元变性（Scale bars=200 μm）

Article: " Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module," by Jie Mou1, Xiaomei Liu2, Dongsheng Pei3 (1 Jiangsu Key Laboratory of Targeted Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; 2 School of Basic Medical Science, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; 3 Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China)

Mou J, Liu XM, Pei DS. Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module . Neural Regen Res. 2014;9(23):2059-2065.

New findings about hippocampal neuronal injury in seizure inhibition

Our previous study showed that glutamate receptor (GluR)6 C terminus-containing peptide

conjugated with the human immunodeficiency virus Tat protein (GluR6)-9c can be delivered into

hippocampal neurons. Prof. Dongsheng Pei, Xuzhou Medical College, China and his

colleagues performed a study to investigate whether glutamic acid receptor 6-PSD-95-MLK3

signaling module was assembled in hippocampal CA1 region in a rat model of kainite-induced

seizure and they found that recombinant adenovirus (Ad) carrying GluR6c could suppress the

assembly of GluR6-PSD95-MLK3 signaling module, inhibit the activation of JNK signal pathway,

and reduce kainite-induced hippocampal neuronal deaths, thereby exhibiting neuroprotective

effects. These findings provide a possible gene therapy of seizure. These results were

published in Neural Regeneration Research (Vol. 9, No. 23, 2014).

Ad-GluR6c injection can obviously alleviate kainite-induced neuronal degeneration (immunohistochemical staining; scale bar: 200 μm)

Article: " Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module," by Jie Mou1, Xiaomei Liu2, Dongsheng Pei3 (1 Jiangsu Key Laboratory of Targeted Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; 2 School of Basic Medical Science, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; 3 Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China)

Mou J, Liu XM, Pei DS. Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module . Neural Regen Res. 2014;9(23):2059-2065.