EXPRESSION OF GAP-43 IN THE GRANULE CELLS OF RAT HIPPOCAMPUS AFTER SEIZURE-INDUCED SPROUTING OF MOSSY FIBERS - IN-SITU HYBRIDIZATION AND IMMUNOCYTOCHEMICAL STUDIES

The axonal growth-associated protein GAP-43 is believed to play some r ole in the synaptic remodelling that takes place in the hippocampus of adult rats after certain experimental lesions. GAP-43 mRNA is highly expressed in adult CA3 pyramidal cells but almost absent in the dentat e granule cells. We analysed whether the sprouting of granule cell axo ns, the messy fibres of the hippocampus, caused by kainic acid-induced seizures in adult rats was associated with any induction of GAP-43 mR NA in granule cells and with any changes in the immunostaining pattern of GAP-43 in the hippocampus. Increased GAP-43 mRNA expression was fo und to be induced in granule cells 18, 24 and 30 h after a systemic in jection of kainic acid which induced generalized seizures in adult rat s, and returned to control levels by 48 h post-treatment. No effect wa s observed in other regions of the hippocampus. However, when kainic a cid was injected into 15-day-old rats, which responded with generalize d seizures but no sprouting of messy fibres, there was no induction of GAP-43 mRNA in the granule cells, suggesting a close relation between GAP-43 expression and sprouting of these cells. Seven days after kain ic acid injections, GAP-43 immunostaining was decreased in the inner m olecular layer of the dentate gyrus except for a thin supragranular ba nd, whereas 30 days after treatment all animals showed increased GAP-4 3 immunoreactivity in the whole inner molecular layer. Since collatera ls of mossy fibres grow in the inner molecular layer after kainic acid -induced seizures, these results support the theory that GAP-43 plays a role in synaptic remodelling in the adult central nervous system.