机构:[1]Department of Neurology, The First Affiliated Hospital ofChongqing Medical University, Chongqing Key Laboratory ofNeurology, 1 YouYi Road, Chongqing 400016, China内科系统神经内科(ICU)重庆医科大学附属第一医院[2]Department of Neurology, The First Affiliated Hospital of XinxiangMedical University, Weihui 453100, China[3]Department of Neurology, The First Affiliated Hospital of KunmingMedical University, Kunming 650032, China内科科室神经内科昆明医科大学附属第一医院[4]Department of Neurology, Affiliated Hospital of North SichuanMedical College, Nanchong 637000, China
Epilepsy is one of the most common and severe neurologic diseases. The mechanisms of epilepsy are still not fully understood. Dock3 (dedicator of cytokinesis 3) is one of the new kinds of guanine-nucleotide exchange factors (GEF) and plays an important role in neuronal synaptic plasticity and cytoskeleton rearrangement; the same mechanisms were also found in epilepsy. However, little is known regarding the expression of Dock3 in the epileptic brain and whether Dock3 interventions affect the epileptic process. In this study, we showed that the expression of Dock3 significantly increased in IE patients and a lithium-pilocarpine epilepsy model compared with the controls. Inhibition of Dock3 by Dock3 shRNA impaired the severity of status epilepticus in the acute stage and decreased the spontaneous recurrent seizures times in the chronic stage of lithium-pilocarpine model and decreased the expression of rac1-GTP. Consistent with decreased expression of Dock3, the latent period in a pentylenetetrazole kindling model also increased. Our results demonstrated that the increased expression of Dock3 in the brain is associated with epileptogenesis and specific inhibition of Dock3 may be a potential target in preventing the development of epilepsy in patients.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30870877, 81071039, 81220108010, 81171197]
第一作者机构:[1]Department of Neurology, The First Affiliated Hospital ofChongqing Medical University, Chongqing Key Laboratory ofNeurology, 1 YouYi Road, Chongqing 400016, China[2]Department of Neurology, The First Affiliated Hospital of XinxiangMedical University, Weihui 453100, China
通讯作者:
推荐引用方式(GB/T 7714):
Li Jie,Mi Xiujuan,Chen Ling,et al.Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models[J].MOLECULAR NEUROBIOLOGY.2016,53(4):2715-2725.doi:10.1007/s12035-015-9406-9.
APA:
Li, Jie,Mi, Xiujuan,Chen, Ling,Jiang, Guohui,Wang, Na...&Wang, Xuefeng.(2016).Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models.MOLECULAR NEUROBIOLOGY,53,(4)
MLA:
Li, Jie,et al."Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models".MOLECULAR NEUROBIOLOGY 53..4(2016):2715-2725