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Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models

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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.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (no. 30870877, no. 81071039, no. 81220108010, and no. 81171197). We sincerely appreciate Xuanwu Hospital, Beijing Tiantan Hospital of the Capital University of Medical Sciences and Daping Hospital of the Third Military Medical University for supplying the surgery samples. We sincerely thank the local ethics committee and the National Institutes of Health of China for their support.

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 YouYi Road, Chongqing, 400016, China

    Jie Li, Xiujuan Mi, Na Wang, Yujiao Zhang, Wanni Deng, Zhihua Wang, Guojun Chen & Xuefeng Wang

  2. Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, China

    Jie Li

  3. Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China

    Ling Chen

  4. Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China

    Guohui Jiang

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  1. Jie Li
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  2. Xiujuan Mi
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Correspondence to Xuefeng Wang.

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Li, J., Mi, X., Chen, L. et al. Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models. Mol Neurobiol 53, 2715–2725 (2016). https://doi.org/10.1007/s12035-015-9406-9

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  • DOI: https://doi.org/10.1007/s12035-015-9406-9

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