Levetiracetam prevents kindling-induced asymmetric accumulation of hippocampal 7S SNARE complexes

Purpose: Understanding the molecular mechanisms underlying epilepsy is crucial to designing novel therapeutic regimens.This report focuses on alterations in the secretory machinery responsible for neurotransmitter (NT) release.Soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptor (SNARE) complexes mediate the fusion of synaptic vesicle and active zone membranes, thus mediating NT secretion.SNARE regulators control where and when SNARE complexes are formed.Previous studies showed an asymmetric accumulation of 7S SNARE complexes (7SC) in the ipsilateral hippocampus of kindled animals.The present studies probe the persistence of 7SC accumulation and the effect of the anticonvulsant, levetiracetam (LEV), on 7SC and SNARE regulators.Method: Quantitative Western blotting was used to monitor levels of 7SC and SNARE regulators in hippocampal synaptosomes from kindled animals both before and after LEV treatment.Results: The asymmetric accumulation of 7SC is present 1-year postamygdalar kindling.The synaptic vesicle protein, synaptic vesicle protein 2 (SV2), a primary LEV-binding protein, and the SNARE regulator Tomosyn increase, whereas NSF decreases in association with this accumulation.Treatment with LEV prevented kindling-induced accumulation of SV2, but did not affect the transient increase of Tomosyn or the long-term decrease NSF.LEV treatment retarded the electrical and behavioral concomitants of amygda-lar kindling coincident with a decrease in accumulation of7SC.Conclusions: The ipsilateral hippocampal accumulation of SNARE complexes is an altered molecular process associated with kindling that appears permanent.Kindling epileptogenesis alters synap-tosomal levels of the SNARE regulators: NSF, SV2, and Tomosyn.Concomitant treatment with LEV reverses the kindling-induced 7SC accumulation and increase ofSV2.copyright