BDNF-TrkB signaling pathway is involved in pentylenetetrazoleevoked progression of epileptiform activity in hippocampal neurons in anesthetized rats

• Published in: Neuroscience bulletin Vol. 29; no. 5; pp. 565 - 575
• Main Authors: Liu, Xu, Liu, Jia, Liu, Juan, Liu, Xiao-Ling, Jin, Ling-Yan, Fan, Wei, Ding, Jin, Peng, Li-Chao, Wang, Yun, Wang, Xin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2013
• Subjects: Anatomy; Anesthesiology; Biomedical and Life Sciences; Biomedicine; Human Physiology; Neurology; Neurosciences; Original; Original Article; Pain Medicine; 信号转导通路; 动物模型; 大鼠; 海马CA1区; 海马神经元; 癫痫; 麻醉; epilepsy; TrkB; hippocampus; BDNF; pentamethylenetetrazole
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-013-1326-y

Pentylenetetrazole（PTZ）is a widely-used convulsant used in studies of epilepsy;its subcutaneous injection generates an animal model with stable seizures.Here,we compared the ability of PTZ via the intravenous and subcutaneous routes to evoke progressive epileptiform activity in the hippocampal CA1 neurons of anesthetized rats.The involvement of the BDNF-TrkB pathway was then investigated.When PTZ was given intravenously,it induced epileptiform bursting activity at a short latency in a dose-dependent manner.However,when PTZ was given subcutaneously,it induced a slowly-developing pattern of epileptogenesis;first,generating multiple population-spike peaks,then spontaneous interictal discharge-like spike,leading to the final ictal discharge-like,highly synchronized bursting firing in the CA1 pyramidal layer of the hippocampus.K252a,a TrkB receptor antagonist,when given by intracerebroventricular injection,significantly reduced the probability of multiple population spike peaks induced by subcutaneous injection of PTZ,delayed the latency of spontaneous spikes,and reduced the burst frequency.Our results indicate that PTZ induces a progressive change of neuronal epileptiform activity in the hippocampus,and the BDNF-TrkB signaling pathway is mainly involved in the early phases of epileptogenesis,but not the synchronized neuronal burst activity associated with epileptic seizure in the PTZ animal model.These results provide basic insights into the changing pattern of hippocampal neuronal activity during the development of the PTZ seizure model,and establish an in vivo seizure model useful for future electrophysiological studies of epilepsy.