Brain-derived neurotrophic factor (BDNF) and the dentate gyrus mossy fibers: Implications for epilepsy

Abstract

This chapter reviews studies of BDNF's effects on mossy fiber transmission that suggest a prominent role for this neurotrophin in regulation of this synapse. BDNF appears to increase the ability of mossy fibers to excite CA3 pyramidal neurons by an action on trkB receptors that leads to altered glutamate release. Under normal conditions, the result may be beneficial, because a slight increase in glutamate release may promote synaptogenesis during development, dendritic spine plasticity, as well as a long-lasting potentiation, analogous to what has been documented in CA 1 (Figure 8). However, too much BDNF may not be beneficial. Excess BDNF may arise following a variety of stimuli, insults, hormonal changes, or activity-induced upregulation. This may ultimately have negative consequences by increasing seizure susceptibility and leading to a chronic elevation in BDNF, similar to what has been detected in epileptic rats and human temporal lobe epilepsy (Figure 8). Under these conditions, any subsequent release of BDNF could trigger seizures theoretically. If correct, this hypothesis suggests that anticonvulsants that block BDNF upregulation or trkB may be a novel therapeutic strategy to treat epilepsy.