To BDNF or Not to BDNF: That Is the Epileptic Hippocampus

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has drawn much attention as a potential therapeutic target for temporal lobe epilepsy (TLE). TLE seizures are produced by synchronized hyperactivity of neuron populations due to the disruption of a balance between excitatory and inhibitory synaptic transmissions. In epileptogenesis-related brain areas, including the hippocampus, BDNF is up-regulated in the course of the development of epilepsy and induces a collapse of balanced excitation and inhibition, eventually exerting its epileptogenic effects. On the other hand, several reports demonstrate that intrahippocampal infusion of BDNF can attenuate (or retard) the development of epilepsy. This antiepileptogenic effect seems to be mediated mainly by an increase in the expression of neuropeptide Y. These contrasting effects of BDNF have prevented us from concluding whether inhibition or enhancement of BDNF signaling finally achieves the prevention of TLE. To address this question, it is essential to evaluate how BDNF changes its influences depending on conditions, for example, cell specificity, neural networks, and expression timing and loci. In this article, the authors review BDNF-induced acute and long-lasting changes seen in epileptic circuits from the anatomical and functional points of view.