Brain-derived Neurotrophic Factor (bdnf) and the Dentate Gyrus Mossy Fibers: Implications for Epilepsy

In the last decade, one of the most avidly studied compounds in the central nervous system (CNS) has been the neurotrophin BDNF. Although historically it had been studied in the context of development, where it plays numerous critical roles, more recent studies have shown striking actions on a number of pathways and processes that are critical for normal function of the adult CNS. In addition, studies of neurological and psychiatric diseases indicate a potential role for BDNF in pathology. Our interest in BDNF began with the demonstration that one of the regions where BDNF protein expression is among the highest in the adult rat brain is the dentate gyrus (Conner et al., 1997; Yan et al., 1997). Previous studies had not clearly defined where BDNF protein was expressed, although mRNA was definitely in hippocampal neurons, and many other adult brain regions. One of the interesting aspects of BDNF protein expression in the dentate gyrus that came to light after the development of specific antibodies was that its location was extremely specific. Thus, in the normal adult rat, hippocampal BDNF protein expression is much greater in the axons of the dentate granule cells, the mossy fibers, than anywhere else in hippocampus. This led us to study mossy fiber BDNF specifically, and the results showed that mossy fiber BDNF has potent functional effects. These studies, and their implications for epilepsy, are reviewed below.