Conditional downregulation of brain- derived neurotrophic factor and tyrosine kinase receptor B blocks epileptogenesis in the human temporal lobe epilepsy hippocampus

Abstract

Brain-derived neurotrophic factor (BDNF) has been implicated as a potential therapeutic target in temporal lobe epilepsy (TLE). However, whether BDNF exerts an epileptogenic or antiepileptogenic function remains controversial. BDNF/tyrosine kinase receptor B (trkB) expression levels were comparatively assessed in the hippocampal tissue of TLE patients with (HS group) and without hippocampal sclerosis (non-HS group) as well as from non-epileptic controls. Immunohistochemistry and immunoblot analysis revealed a marked increase in BDNF/trkB expression in the dentate gyrus and CA3 regions of HS and non-HS groups. The lack of any differences in expression levels was observed between HS and non-HS patients. Meanwhile, treatment with VPA (Valproic acid, anti-epileptic drug) resulted in a significant down-regulation of BDNF/trkB protein expression in sclerotic and non-sclerotic hippocampus (P < 0.001). In contrast, no marked change was noticed in VPA-untreated and OA-treated groups (sodium octanoate). These results suggest that the up-regulation of BDNF/trkB pathway might be at least in part responsible for the epileptogenesis.