Abstracts

Reelin is a large secreted glycoprotein that has important roles in the developing nervous system as well as in the adult nervous system. It is believed that extracellular reelin may act as either a stop or as a chemoattracting signal for radially migrating neurons. Deficits in reelin signaling have been found in a variety of neurodevelopment and neurodegenerative disorders, including epilepsy. However, in the adult nervous system, the specific role of reelin is not fully understood. Reelin is synthesized and released by GABAergic interneurons and recent studies have suggested that reelin might modulate and even enhance long-term potentiation in the adult brain. Importantly, enhancement in synaptic transmission is thought to play a crucial role in the intensification of afterdischarges and progressive development of convulsions in the amygdala kindling model of epilepsy., To determine if amygdala kindling was associated with changes in reelin expression, rats were surgically implanted with an electrode into the basolateral amygdala and subjected to 99 kindled or sham stimulations. An additional group of non-kindled genetically prone FAST kindled rats was also processed in order to determine if basal reelin expression was altered in rats that were genetically more susceptible to enhanced amygdaloid excitability and the effects of kindling. Brains were processed for immunohistochemical determination of reelin, NeuN, and doublecortin., The total number of reelin positive cells in the hilus was not substantially different between all groups; however, there was a slight decrease in the number of these cells within the subgranular zone for the kindled and non-kindled FAST rats. A decrease in reelin expression within the stratum lacunosum-moleculare was also found for kindled and non-kindled FAST rats. Doublecortin immunohistochemistry revealed that some newly born neurons migrated ectopically into the hilus for kindled rats but not for sham-stimulated controls or for non-kindled FAST rats. Interestingly, we often observed several abnormally located reelin positive cells scattered throughout the dentate granule cell layer for non-kindled FAST rats suggesting a possible pre-existing GABAergic circuit malformation in this group of rats., These findings suggest that changes in reelin expression within the hippocampus during development might influence network formation that may influence susceptibility to epilepsy., (Supported by NSERC.)