Selective Upregulation of Brain-Derived Neurotrophic Factor (BDNF) Transcripts and BDNF Direct Induction of Activity Independent N -Methyl-D-Aspartate Currents in Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis

Abstract

Brain-derived neurotrophic factor (BDNF) plays a critical role in many aspects of neuronal biology and hippocampal physiology and pathology, and has been implicated as a potential therapeutic target in temporal lobe epilepsy (TLE). BDNF total mRNA and its six transcripts were compared in the hippocampal tissue of TLE patients with or without hippocampal sclerosis (HS) by real-time fluorescence quantitative polymerase chain reaction. Excitatory actions induced by BDNF on hippocampal cells were investigated by whole-cell patch-clamp recordings. Statistically significant increases in three human BDNF mRNA transcripts were observed in TLE patients with HS compared with those without HS (transcripts 2, 3 and 5 exhibited 2.1-, 2.3-and 4.1-fold increases, respectively); there were no significant increases in other transcripts. BDNF directly induced N-methyl-d-aspartate currents in dentate granule cells of TLE patients with HS. These results demonstrated that BDNF transcripts were selectively upregulated in TLE patients with HS compared with those without HS. Moreover, BDNF induced excitability of dentate granule cells in TLE patients with HS.