Expression of c-fos mRNA after cortical ablation in rat brain is modulated by basic fibroblast growth factor (bFGF) and the NMDA receptor is involved in c-fos expression.
Expression of c-fos mRNA after cortical injury was studied using the in situ hybridization technique. Strong signals for c-fos mRNA were observed immediately after cortical ablation in neurons throughout the cortex ipsilateral to the injury. However, this c-fos mRNA expression was transient and disappeared within 6 h after the injury. When basic fibroblast growth factor (bFGF; 1 micrograms) was applied to the site of ablation, c-fos mRNA signals were observed for a much longer period. Even 24 h after injury, diffuse expression of c-fos mRNA was detected throughout the cortex, being mainly confined to non-neuronal cells. Intraperitoneal injection of MK-801 (3 mg/kg), a non-competitive NMDA receptor antagonist, suppressed the expression of c-fos mRNA after cortical ablation. It suppressed both the immediate and late expression induced by cortical ablation and bFGF. The immediate expression of c-fos in neurons is likely to be due to spreading depression, while neuronal-glial interactions would be involved in the mechanism of late c-fos expression by non-neuronal cells. Our results suggest that induction of c-fos after cortical injury can be modulated by topically applied bFGF and that the N-methyl-D-aspartate (NMDA) receptor is involved in c-fos expression not only caused by injury itself but also induced by injury and bFGF. As the immediate early genes regulate secondary gene responses, the induction of c-fos may contribute to neuronal plasticity and bFGF may enhance its effect.
Kohmura
E
E
Department of Neurosurgery, Osaka University Medical School, Japan.
Yuguchi
T
T
Yamada
K
K
Sakaguchi
T
T
Wanaka
A
A
Hayakawa
T
T
D000818:Animals; D001921:Brain / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D017403:In Situ Hybridization; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016222:Fibroblast Growth Factor 2; D016291:Dizocilpine Maleate