Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models

• Published in: Molecular neurobiology Vol. 53; no. 4; pp. 2715 - 2725
• Main Authors: Li, Jie, Mi, Xiujuan, Chen, Ling, Jiang, Guohui, Wang, Na, Zhang, Yujiao, Deng, Wanni, Wang, Zhihua, Chen, Guojun, Wang, Xuefeng
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2016; Springer Nature B.V
• Subjects: Action Potentials; Adolescent; Adult; Animals; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Brain research; Cell Biology; Convulsions & seizures; Cytoskeleton; Disease Models, Animal; Down-Regulation; Epilepsy; Epilepsy - metabolism; Epilepsy - physiopathology; Excitatory Postsynaptic Potentials; Female; Green Fluorescent Proteins - metabolism; Guanine Nucleotide Exchange Factors - metabolism; Guanosine Triphosphate - metabolism; Hospitals; Humans; Immunohistochemistry; Lithium; Male; Mice, Inbred C57BL; Mossy Fibers, Hippocampal - pathology; Nerve Tissue Proteins - metabolism; Neurobiology; Neurology; Neurons - metabolism; Neurons - pathology; Neurosciences; Patients; Pilocarpine; Proteins; rac1 GTP-Binding Protein - metabolism; Rats, Sprague-Dawley; RNA, Small Interfering - metabolism; Signal Transduction; Young Adult; China; rac1; Epileptogenesis; Dedicator of cytokinesis 3; Epilepsy
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-015-9406-9

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.