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

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 ( T rk B ) are believed to be critical for epileptogenesis. Previous studies have revealed possible changes in the expression of full‐length T rk B receptors ( T rk B . FL ) and truncated T rk B receptors ( T rk B . T ) in neurodegenerative disorders. In this study, we investigated alterations in T rk B receptor expression and T rk B signalling activity in a rat hippocampal neuronal model of spontaneous recurrent epileptiform discharges ( SRED s) and the effects on the epileptiform discharges. To induce epileptiform discharges, we established a model with M g 2+ ‐free treatment. We found a dramatic upregulation of T rk B . T and a decrease in T rk B . FL in the SRED s model. Calpain contributed to the downregulation of T rk B . FL . The upregulation of T rk B . T required transcription and translation activity. Furthermore, BDNF induced the activation of T rk B . FL signalling. However, T rk B . FL signalling was inhibited in the SRED s model. Although calpain inhibitors prevented a decrease in T rk B . FL , they did not restrain the downregulation of T rk B . FL signalling activity in the model. However, a SRED s model with a translation inhibitor prevented the increase in T rk B . T and re‐activated T rk B . FL signalling activity. Finally, we used electrophysiology to observe that a downregulation of T rk B . T could relieve the representative epileptiform discharges in the model. These results, taken together, demonstrate that alterations in T rk B . FL signalling may be regulated via T rk B . T receptors. Upregulation of T rk B . FL signalling suppresses epileptiform discharges in the SRED s model.