Induction of F1/GAP-43 gene expression in hippocampal granule cells after seizures [corrected]

In the adult rat hippocampus mRNA of F1/GAP-43, an axonal growth-associated protein, is highly expressed in pyramidal cells, but is absent in granule cells. To determine whether granule cells can be induced to express mRNA of F1/GAP-43, transcript levels were studied after limbic seizures, which can induce sprouting of granule cell mossy fibers. Seizure-inducing electrolytic lesions were made in the dentate gyrus hilus with stainless-steel electrodes and mRNA levels were measured in contralateral hippocampus by quantitative in situ hybridization. Induction of F1/GAP-43 mRNA expression was observed in granule cells at 24 h, but not at 6 or 12 h, after the hilar lesion. When equivalent sized hilar lesions were made with platinum electrodes, which do not induce seizures, no hybridization was apparent over the granule cells. Hybridization over granule cells had declined by 48 h post-lesion, but even at 10 days it was still slightly higher than in control rats. F1/GAP-43 mRNA expression was also increased 2-fold in CA1 pyramidal cells with peak expression at 48 h post-lesion. These are the first data to our knowledge that demonstrate that F1/GAP-43 gene expression can be altered in neurons located within the adult brain. Induction of F1/GAP-43 mRNA expression in the granule cells may be important for the sprouting of mossy fibers and could be triggered by the elevated levels of brain-derived neurotrophic factor in CA3 cells which precede the increased F1/GAP-43 gene expression in granule cells.