PMID- 10999533 OWN - NLM STAT- MEDLINE DCOM- 20001017 LR - 20220129 IS - 0013-9580 (Print) IS - 0013-9580 (Linking) VI - 41 Suppl 6 DP - 2000 TI - Different patterns of induction of fibroblast growth factor-2 and brain-derived neurotrophic factor messenger RNAs during kindling epileptogenesis, and development of a herpes simplex vector for fibroblast growth factor-2 gene transfer in vivo. PG - S122-6 AB - PURPOSE: To investigate the gene expression patterns of brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF-2) in the kindling model, and to construct a replication-defective herpes simplex virus vector to induce expression of FGF-2 in vivo. METHODS: RNase protection assay and herpes simplex virus vector (TH FGF-2) deleted in the immediate-early genes ICP4, ICP22, and ICP27, with FGF-2 inserted in tk under the control of the human cytomegalovirus immediate-early promoter. RESULTS: A single kindling stimulation did not modify BDNF gene expression, whereas it increased FGF-2 messenger RNA (mRNA) levels in the hippocampus, the cortex, and the hypothalamus. BDNF and FGF-2 gene expression were not altered in kindled animals left unstimulated for 1 week. In contrast, kindled seizures produced a great increase in hippocampal and cortical BDNF mRNA levels, but FGF-2 mRNA was increased only in the ipsilateral cortex. Infection of Vero cells with TH FGF-2 resulted in a long-lasting increase in FGF-2 levels. Protein extracts of infected cells induced neuronal differentiation of PC12 cells, indicating that the newly synthesized FGF-2 was biologically active. Robust transient transgene expression was observed in the rat hippocampus after inoculation with TH FGF-2 in the absence of significant toxicity. CONCLUSIONS: BDNF and FGF-2 are recruited at different stages of kindling and, accordingly, may play different roles in the adaptive changes taking place during epileptogenesis. TH FGF-2 is suitable for studies of FGF-2 involvement in kindling epileptogenesis. FAU - Bregola, G AU - Bregola G AD - Department of Experimental and Clinical Medicine, Biotechnology Center, University of Ferrara, Italy. FAU - Frigati, L AU - Frigati L FAU - Zucchini, S AU - Zucchini S FAU - Simonato, M AU - Simonato M LA - eng GR - E.0954/TI_/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/*metabolism MH - Defective Viruses/genetics MH - Epilepsy/chemically induced/*genetics/*metabolism MH - Fibroblast Growth Factor 2/*genetics/*metabolism MH - Gene Expression MH - *Gene Transfer Techniques MH - Genetic Vectors/genetics MH - Hippocampus/chemistry/metabolism MH - In Situ Hybridization MH - Kindling, Neurologic/*metabolism MH - Male MH - RNA, Messenger/analysis/biosynthesis/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Simplexvirus/*genetics MH - Transgenes/genetics EDAT- 2000/09/22 11:00 MHDA- 2000/10/21 11:01 CRDT- 2000/09/22 11:00 PHST- 2000/09/22 11:00 [pubmed] PHST- 2000/10/21 11:01 [medline] PHST- 2000/09/22 11:00 [entrez] AID - 10.1111/j.1528-1157.2000.tb01570.x [doi] PST - ppublish SO - Epilepsia. 2000;41 Suppl 6:S122-6. doi: 10.1111/j.1528-1157.2000.tb01570.x.