RELATIONSHIP BETWEEN GAP-43 EXPRESSION IN THE DENTATE GYRUS AND SYNAPTIC REORGANIZATION OF HIPPOCAMPAL MOSSY FIBERS IN RATS TREATED WITH KAINIC ACID

Kainic acid-induced seizures in adult rats produce neurodegeneration i n the hippocampus followed by sprouting of the messy fibres in the inn er molecular layer of the dentate gyrus and changes in GAP-43 expressi on in the granule cells. In the present study we observed that 4 days after kainic acid injection a dense plexus of silver-impregnated degen erating terminals detected by Gallyas's method and a decrease of GAP-4 3 immunostaining was observed in the inner molecular layer of the dent ate gyrus indicating deafferentiation of this region. This was associa ted with the formation of an intense GAP-43 immunostained band in the supragranular layer. MK-801, a non-competitive inhibitor of the NMDA r eceptor, which partially inhibited the behavioural seizures induced by KA, also protected from the inner molecular layer deafferentation and markedly reduced the expression of GAP-43 mRNA in the granule cells a nd the intense GAP-43 immunostained band in the supragranular layer, s uggesting a relationship among these events. Two months after kainic a cid injection the intense supragranular GAP-43 positive band was no lo nger evident but the whole inner molecular layer appeared more labelle d in association with the formation of the collateral sprouting of the messy fibres in the inner molecular layer as detected by Timm's stain ing. These effects were also markedly reduced by the pretreatment with MK-801. Taken together, these experiments indicate for the first time a direct relationship between the increase of GAP-43 immunostaining i n the inner molecular layer of the dentate gyrus and the collateral sp routing of messy fibres in this district in response to kainic acid in duced seizures. This further supports the hypothesis that the early in duction of GAP-43 in granule cells may be one of the molecular mechani sms required for the synaptic reorganization of the mossy fibres.