Molecular Basis of Synaptic Reorganization in Focal Epilepsy

Mossy fiber sprouting and other forms of synaptic reorganization may form the basis for a recurrent excitatory network in epileptic foci. Four major classes of axon guidance molecules, the ephrins, netrins, slits, and semaphorins provide targeting information to outgrowing axons along predetermined pathways during development. These molecules may also play role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. We studied semaphorin gene expression as assessed by in situ hybridization using riboprobes generated from rat cDNA in an adult model of synaptic reorganization, kainic acid (KA) induced status epilepticus (SE). Within the first week after KA induced SE, Semaphorin 3C, a class III semaphorin, mRNA content is decreased in CAl area of hippocampus and increased in the upper layers of cerebral cortex. Another class III semaphorin, Semaphorin 3F, is also decreased in CAI and CA3 of hippocampus within the first week after KA-SE. These changes in gene expression are confined principally to neurons. By contrast, there was little change in semaphorin 4C mRNA content of CAl neurons at this time. No changes in expression of semaphorin 3A and 4C genes were detected 28 days after KA induced SE. Regulation of semaphorin gene expression following KA induced SE suggests that neurons may regulate the expression of axonal guidance molecules and thereby contribute to synaptic reorganization after injury of the mature brain. The anatomic locale of the altered semaphorin gene expression may serve as a marker for specific networks undergoing synaptic reorganization in epileptic brain.