Epileptogenesis and epilepsy progression are associated with rearrangements of neuronal circuits mediated by such processes as sprouting, neuronal cell death, and neurogenesis. These processes lead to hyperexcitability, spontaneous seizures, and/or worsening of seizure severity/frequency. Neurotrophic factors, and the Fibroblast Growth Factor-2 (FGF-2) in particular, are mediators for these reorganizational processes, and thus may play a role in epileptic phenomena. In this article, we will summarize and discuss the data supporting this hypothesis. Experimental evidence demonstrates that: 1) Seizures increase FGF-2 mRNA and protein levels in specific brain areas, and up-regulate the expression of the FGF-2 high-affinity receptor, FGFR-1; 2) Acute injection of FGF-2 causes seizures, while chronic infusion of low dose FGF-2 does not affect kainate-induced seizures but reduces hippocampal damage; 3) Kainate-induced seizure severity is not altered in FGF-2 knock-out mice, but is increased in FGF-2 over-expressing mice. Thus, FGF-2 may be implicated in seizure susceptibility and in seizure-induced plasticity, exerting two different, and apparently contrasting effects - favoring ictogenesis but reducing seizure-induced cell death. Dissecting out the mechanisms underlying these effects will be critical in pursuing the goal of controlling seizures and their deleterious consequences through modulation of the FGF-2 system.
Fibroblast Growth Factor-2 (FGF-2).
SIMONATO, Michele;ZUCCHINI, Silvia
2009
Abstract
Epileptogenesis and epilepsy progression are associated with rearrangements of neuronal circuits mediated by such processes as sprouting, neuronal cell death, and neurogenesis. These processes lead to hyperexcitability, spontaneous seizures, and/or worsening of seizure severity/frequency. Neurotrophic factors, and the Fibroblast Growth Factor-2 (FGF-2) in particular, are mediators for these reorganizational processes, and thus may play a role in epileptic phenomena. In this article, we will summarize and discuss the data supporting this hypothesis. Experimental evidence demonstrates that: 1) Seizures increase FGF-2 mRNA and protein levels in specific brain areas, and up-regulate the expression of the FGF-2 high-affinity receptor, FGFR-1; 2) Acute injection of FGF-2 causes seizures, while chronic infusion of low dose FGF-2 does not affect kainate-induced seizures but reduces hippocampal damage; 3) Kainate-induced seizure severity is not altered in FGF-2 knock-out mice, but is increased in FGF-2 over-expressing mice. Thus, FGF-2 may be implicated in seizure susceptibility and in seizure-induced plasticity, exerting two different, and apparently contrasting effects - favoring ictogenesis but reducing seizure-induced cell death. Dissecting out the mechanisms underlying these effects will be critical in pursuing the goal of controlling seizures and their deleterious consequences through modulation of the FGF-2 system.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
