SYNAPTIC REORGANIZATION FOLLOWING KAINIC ACID-INDUCED SEIZURES DURINGDEVELOPMENT

Prolonged seizures in the adult brain causes neuronal loss in the hipp ocampus and aberrant growth (sprouting) of granule cell axons (mossy f ibers) in the supragranular zone of the fascia dentata and stratum inf rapyramidale of CA3. There is considerable evidence that these changes in neuronal growth following seizures are age related, with younger a nimals having fewer reactive changes following prolonged seizures than older animals. However, there is little information available regardi ng the age at which seizures in the developing brain result in alterat ions in axonal growth and synapse formation. In this study, we evaluat ed the effects of kainic acid (KA)-induced seizures during development on synaptic reorganization using the expression of growth-associated protein-43 (GAP-43), a marker for synaptogenesis and Timm stain which detects the presence of zinc in granule cell axons, Age specific doses of KA were used to induce seizures of similar intensity at various ag es (postnatal days (P) 12, 21, 25, 35, 45, 60) in Sprague-Dawley rats. Up to the age of P25, there were no differences in either Timm or GAP -43 staining between animals with KA seizures and controls. In P25 and older KA-treated rats, Timm staining was found in the supragranular l ayer of the dentate gyrus. This staining increased with age at the tim e of KA injection. Seizures in adult (P60), but not younger rats also resulted in increased staining in the suprapyramidal layer of the CA3 subfields. Changes in GAP-43 were delayed compared to the Timm stainin g with no differences between KA-treated animals and controls until P3 5 when a band of GAP-43 were delayed compared to the Timm staining wit h no differences between KA-treated animals and controls intensity and thickness with time. This study demonstrates that seizure-induced rea ctive synaptogenesis is age-related. Since both Timm and GAP-43 reflec t different aspects of reactive synaptogenesis, used in combination th ese methods provide useful information about the structural changes fo llowing seizures during development. (C) 1998 Elsevier Science B.V.