PMID- 14643774 OWN - NLM STAT- MEDLINE DCOM- 20040304 LR - 20190712 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 122 IP - 4 DP - 2003 TI - Exacerbated status epilepticus and acute cell loss, but no changes in epileptogenesis, in mice with increased brain-derived neurotrophic factor signaling. PG - 1081-92 AB - Several studies suggest that brain-derived neurotrophic factor (BDNF) can exacerbate seizure development during status epilepticus (S.E.) and subsequent epileptogenesis in the adult brain. On the other hand, evidence exists for the protective effect of BDNF. To study this controversy, we induced S.E. with kainate in transgenic mice with increased BDNF signaling due to trkB overexpression. Transgenic mice experienced a more severe S.E. than wild type animals did. Furthermore, they had increased acute hippocampal neuronal loss when assessed at 48 h after S.E. The effect of trkB overexpression on the development of epilepsy, chronic neuronal death, mossy fiber sprouting, and neurogenesis were studied at 4.5 months after kainate-induced S.E. No differences were found in the rate of epileptogenesis, severity of epilepsy, or cellular markers of network reorganization between transgenic and wild type mice. No differences between genotypes were observed in TUC-4 staining, indicating no effect of trkB overexpression to immature neuron numbers. Instead, in Cresyl Violet-stained preparations, the highest density of neurons was found in untreated transgenic mice suggesting a favorable effect of trkB overexpression on the survival of neurons in the hippocampus. Our data support the role of BDNF and trkB signaling in seizure generation and acute cellular damage after S.E. Long-term outcome was not, however, exacerbated by trkB overexpression. FAU - Lahteinen, S AU - Lahteinen S AD - Laboratory of Molecular Pharmacology, A I Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland. FAU - Pitkanen, A AU - Pitkanen A FAU - Koponen, E AU - Koponen E FAU - Saarelainen, T AU - Saarelainen T FAU - Castren, E AU - Castren E LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Cell Count/methods MH - Humans MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred DBA MH - Mice, Transgenic MH - Receptor, trkB/*biosynthesis/genetics MH - Signal Transduction/*physiology MH - Status Epilepticus/genetics/*metabolism/pathology EDAT- 2003/12/04 05:00 MHDA- 2004/03/05 05:00 CRDT- 2003/12/04 05:00 PHST- 2003/12/04 05:00 [pubmed] PHST- 2004/03/05 05:00 [medline] PHST- 2003/12/04 05:00 [entrez] AID - S0306452203006845 [pii] AID - 10.1016/j.neuroscience.2003.08.037 [doi] PST - ppublish SO - Neuroscience. 2003;122(4):1081-92. doi: 10.1016/j.neuroscience.2003.08.037.