Decreased BDNF signalling in transgenic mice reduces epileptogenesis.
Brain derived neurotrophic factor (BDNF) has been suggested to be involved in epileptogenesis. Both pro- and antiepileptogenic effects have been reported, but the exact physiological role is still unclear. Here, we investigated the role of endogenous BDNF in epileptogenesis by using transgenic mice overexpressing truncated trkB, a dominant negative receptor of BDNF. After induction of status epilepticus (SE) by kainic acid, the development of spontaneous seizures was monitored by video-EEG system. Hilar cell loss, and the number of neuropeptide Y immunoreactive cells were studied as markers of cellular damage, and mossy fibre sprouting was investigated as a plasticity marker. Our results show that transgenic mice had significantly less frequent interictal spiking than wild-type mice, and the frequency of spontaneous seizures was lower. Furthermore, compared to wild-type animals, transgenic mice had less severe seizures with later onset and mortality was lower. In contrast, no differences between genotypes were observed in any of the cellular or plasticity markers. Our results suggest that transgenic mice with decreased BDNF signalling have reduced epileptogenesis.
Lähteinen
Sari
S
Laboratory of Molecular Pharmacology, A.I.Virtanen Institute, University of Kuopio, Kuopio, Finland.
Pitkänen
Asla
A
Saarelainen
Tommi
T
Nissinen
Jari
J
Koponen
Eija
E
Castrén
Eero
E
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity / Q000235:genetics*; D009478:Neuropeptide Y / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D009478:Neuropeptide Y; D020813:Receptor, trkB