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The suppression of epileptiform discharges in cultured hippocampal neurons is regulated via alterations in full-length tropomyosin-related kinase type B receptors signalling activity

Authors

  • Wei Xie,

    1. School of Biomedical Engineering, Tianjin Medical University, Tianjin, China
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  • Yi-Jun Song,

    Corresponding author
    1. Department of Neurology, Tianjin Medical University General Hospital & Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China
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  • Dai Li,

    1. Senior Officials Inpatient Ward, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China
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  • Li-Ping Pan,

    1. Department of Neurology, Tianjin Medical University General Hospital & Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China
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  • Qiu-Jing Wu,

    1. Department of Neurology, Tianjin Medical University General Hospital & Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China
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  • Xin Tian

    Corresponding author
    1. School of Biomedical Engineering, Tianjin Medical University, Tianjin, China
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Abstract

Epilepsy is a common neurological disease. Understanding the mechanisms of epileptogenesis at the cellular and molecular levels may provide novel targets for preventing this disorder. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase type B (TrkB) are believed to be critical for epileptogenesis. Previous studies have revealed possible changes in the expression of full-length TrkB receptors (TrkB.FL) and truncated TrkB receptors (TrkB.T) in neurodegenerative disorders. In this study, we investigated alterations in TrkB receptor expression and TrkB signalling activity in a rat hippocampal neuronal model of spontaneous recurrent epileptiform discharges (SREDs) and the effects on the epileptiform discharges. To induce epileptiform discharges, we established a model with Mg2+-free treatment. We found a dramatic upregulation of TrkB.T and a decrease in TrkB.FL in the SREDs model. Calpain contributed to the downregulation of TrkB.FL. The upregulation of TrkB.T required transcription and translation activity. Furthermore, BDNF induced the activation of TrkB.FL signalling. However, TrkB.FL signalling was inhibited in the SREDs model. Although calpain inhibitors prevented a decrease in TrkB.FL, they did not restrain the downregulation of TrkB.FL signalling activity in the model. However, a SREDs model with a translation inhibitor prevented the increase in TrkB.T and re-activated TrkB.FL signalling activity. Finally, we used electrophysiology to observe that a downregulation of TrkB.T could relieve the representative epileptiform discharges in the model. These results, taken together, demonstrate that alterations in TrkB.FL signalling may be regulated via TrkB.T receptors. Upregulation of TrkB.FL signalling suppresses epileptiform discharges in the SREDs model.

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