Details

Autor(en) / Beteiligte

• Xie, Wei
• Song, Yi-Jun
• Li, Dai
• Pan, Li-Ping
• Wu, Qiu-Jing
• Tian, Xin

Titel

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

Ist Teil von

• The European journal of neuroscience, 2014-08, Vol.40 (3), p.2564-2575

Ort / Verlag

Oxford: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Access via Wiley Online Library

Beschreibungen/Notizen

• 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. In a rat hippocampal neuronal spontaneous recurrent epileptiform discharges (SREDs) model, we observed the truncated TrkB receptors (TrkB.T) were upregulated and the full‐length TrkB receptors (TrkB.FL) were downregulated. However, the drop in TrkB.T activated the phosphorylation of TrkB.FL and relieved the representative epileptiform discharges in the SREDs model. Therefore, the upregulation of TrkB.FL signalling suppressed the epileptiform discharges in the SREDs model via the drop in TrkB.T.