Abstract

Brain-Derived Neurotrophic Factor Enhances Fast Excitatory Synaptic Transmission in Human Epileptic Dentate Gyrus Zhu WJ, Roper SN Ann Neurol 2001;50:188–194 Purpose Brain-derived neurotrophic factor (BDNF) has trophic effects and modulates synaptic transmission in the hippocampal formation in animal studies. It also is upregulated in acute and chronic epilepsy models and in human temporal lobe epilepsy. This study was undertaken to examine the effects of BDNF on fast synaptic transmission in the human epileptic dentate gyrus. Methods Hippocampal specimens were acquired from patients with temporal lobe epilepsy during surgical removal of the anterior temporal lobe, intended to treat the epileptic condition. Whole-cell patch-clamp recordings were obtained from dentate granule cells in transverse hippocampal slices in vitro. Results Application of BDNF increased the amplitude and frequency of spontaneous excitatory postsynaptic currents and increased the amplitude of evoked excitatory postsynaptic currents. BDNF had no effect on spontaneous inhibitory postsynaptic currents but produced a decrease in amplitude of evoked inhibitory postsynaptic currents. The effects of BDNF were abolished by coapplication of the tyrosine kinase inhibitor K252a; therefore, BDNF enhances fast excitatory transmission in the epileptic human dentate gyrus and may play an important role in epileptogenesis in temporal lobe epilepsy. Conclusions This raises the possibility of designing therapies for this disorder that may be both anticonvulsant and antiepileptogenic.

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