Abstracts

RATIONALE: Brain-derived neurotrophic factor (BDNF) is found in high levels in the hippocampus and is up-regulated in some animal models of epilepsy. BDNF mRNA levels are also increased in dentate granule cells from human patients with temporal lobe epilepsy (Murray et al., 2000). There is evidence from animal studies that BDNF may enhance fast excitatory synaptic transmission in the hippocampus. This study examined the effect of acute application of BDNF on in vitro hippocampal slices from humans with temporal lobe epilepsy. METHODS: 300 ?m-thick transverse hippocampal slices were obtained from 6 patients undergoing anterior temporal lobectomy for intractable temporal lobe epilepsy. Whole cell patch clamp recordings were obtained from visualized dentate granule cells before and during bath application of BDNF, 100 ng/ml. RESULTS: Spontaneous excitatory postsynaptic currents (EPSC's) showed a significant increase in amplitude (12.8 ? 0.26 vs 16.4 ? 0.77 pA, mean ? S.E.M.) and frequency (1.6 ? 0.44 vs 3.9 ? 0.36 Hz) after exposure to BDNF (N=9 cells). Review of data from individual cells demonstrated this response in 8 of 9 cells. Co-application of the tyrosine kinase inhibitor, K252a, abolished the effects of BDNF on spontaneous EPSC's (N=5 cells). BDNF also produced a signficant increase in the amplitude of evoked EPSC's (103.7 ? 7.2 vs 162.4 ? 4.7 pA)(N=9 cells). CONCLUSIONS: In addition to a role in initiating and sustaining synaptic reorganization, BDNF may have a direct role in modulating fast excitatory trasnmission in the human epileptic dentate gyrus.