Brain-derived neurotrophic factor in the development of epilepsy

Epilepsy is one of the most common neurological diseases, but our understanding of the detailed cellular and molecular mechanisms underlying it remains incomplete. Several pathological changes typically occur in the epileptic brain, including neuronal loss, neurogenesis, neurite growth, and reorganization of extracellular matrix leading to changes in neuronal networks. Many of these features are normally regulated by neurotrophic growth factors, especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF modifies both excitatory and inhibitory synaptic transmission in the brain. Therefore, BDNF signaling is an intriguing candidate for playing a role in seizures and epileptogenesis. However, its effects to the development of epilepsy are unknown, although the knowledge of the mechanisms underlying might allow better seizure control and possibly even prevention of epileptogenesis. The aim of this study was to clarify the role of BDNF signaling in different phases of epilepsy. As a model, two transgenic mouse lines with opposite effects to BDNF signaling were used, and epileptogenesis was induced with kainate model of temporal lobe epilepsy. The severity of status epilepticus, development of epileptogenesis, and the severity of epilepsy were monitored with combined video-EEG recordings and histological markers were studied. Moreover, the mechanisms of BDNF action during epileptogenesis were assessed. We extended the previous result by showing that BDNF signaling exacerbates both the severity of status epilepticus and the acute neuronal death. In the later phase, increased BDNF signaling promoted and decreased BDNF signaling reduced the development of epilepsy. Moreover, reduced BDNF signaling showed a disease-modifying role, alleviating the severity of epilepsy. BDNF signaling also increased its own synthesis during status epilepticus, and affected the expression of several functional groups during epileptogenesis; those include cytoskeletal and growth-related proteins, DNA repair, DNA recombination and neuronal death. This suggests that BDNF may regulate several significant processes via trkB receptors during the development of epilepsy. Furthermore, BDNF was shown to be a prominent player in all phases of epileptogenesis, and therefore it might be a useful target for the development of improved anti-epileptic drugs. National Library of Medicine Classification: WL 385, WL 104 Medical Subject Headings: epilepsy, temporal lobe; seizures; status epilepticus; brain-derived neurotrophic factor; receptor, trkB; hippocampus; mice, transgenic; kainic acid; neurons; cell death; gene expression; oligonucleotide array sequence analysis; computational biology Work like you don't need the money. Love like you've never been hurt. Dance like nobody's watching. Live like it's Heaven on Earth.