Seizure-associated induction of basic fibroblast growth factor and its receptor in the rat brain.
In order to assess the role of neuronal activity in the regulation of the fibroblast growth factor system, we examined changes in levels of basic fibroblast growth factor and the expression of its receptor-1 following seizures. Epileptiform activity was induced by kainate injection and the rats displaying seizures were killed 3, 6, 12 and 24 h after injection. To identify basic fibroblast growth factor and fibroblast growth factor receptor-1 immunoreactivity, we used a monoclonal antibody that binds to the biological active form of basic fibroblast growth factor and a monoclonal antibody that recognizes fibroblast growth factor receptor-1. In normal brain tissue, fibroblast growth factor staining was widely distributed throughout the brain and appeared to be localized within the nucleus of astrocytes. Starting 6 h after seizures, there was a progressive increase in basic fibroblast growth factor immunoreactivity. The seizure-induced effect on basic fibroblast growth factor immunoreactivity was expressed in astrocytes as an enlargement of the nucleus and a spreading of the staining to the processes. This phenomenon was particularly strong in the cerebral cortex and hippocampus. The fibroblast growth factor receptor-1 immunoreactivity was virtually absent in control brain tissue. By 3 h post-seizure induction, there was an increase in fibroblast growth factor receptor-1 immunoreactivity in the molecular layer of the dentate gyrus. After 6 h, fibroblast growth factor receptor-1-positive cells appeared in the stratum oriens along the CA1, CA2 and CA3 hippocampal subfields. This effect gradually expanded to other brain regions and by 24 h fibroblast growth factor receptor-1 immunoreactivity was distributed throughout the hippocampus and cerebral cortex. Fluorescent double labelling indicated that the fibroblast growth factor receptor-1 immunoreactivity was expressed in astrocytes. At 24 h, some fibroblast growth factor receptor-1 immunoreactivity was also observed in neuron-like cells located throughout the cerebral cortex and hippocampus. Since our results indicate that seizure activity modulates the expression of basic fibroblast growth factor and fibroblast growth factor receptor-1 levels, it is also possible that physiological stimulation might have similar effects. In addition, our results suggest that the fibroblast growth factor system may have a role in plasticity events triggered by physiological activity.
Van Der Wal
E A
EA
IRU in Brain Aging, University of California, Irvine 92717-4550.
Gómez-Pinilla
F
F
Cotman
C W
CW
D000818:Animals; D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D012016:Reference Values; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D007608:Kainic Acid