title: Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models.
abstract: 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.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.|Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, China.
authors: Jie
authors: J
authors: Li
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.
authors: Xiujuan
authors: X
authors: Mi
authors: Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
authors: Ling
authors: L
authors: Chen
authors: Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
authors: Guohui
authors: G
authors: Jiang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.
authors: Na
authors: N
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.
authors: Yujiao
authors: Y
authors: Zhang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.
authors: Wanni
authors: W
authors: Deng
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.
authors: Zhihua
authors: Z
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China.
authors: Guojun
authors: G
authors: Chen
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China. wxf001239@163.com.
authors: Xuefeng
authors: X
authors: Wang
mesh_terms: D000200:Action Potentials; D000293:Adolescent; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008094:Lithium; D008297:Male; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010862:Pilocarpine; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C485840:DOCK3 protein, human; C000613073:Dock3 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D010862:Pilocarpine; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; D008094:Lithium; D020830:rac1 GTP-Binding Protein
keywords: Dedicator of cytokinesis 3; Epilepsy; Epileptogenesis; rac1