NEUROTRANSMITTER FUNCTION | Presynaptic Neurotransmission: Alterations in Exocytotic/Secretory Machinery in Kindling

Abstract

In molecular terms, epilepsy is a dysfunction in neurotransmission, involving either an inappropriate response to, or an altered release of, neurotransmitters (NT). We have examined the synaptosomal proteins involved in NT release to determine if alterations in their interactions correlate with epilepsy. We have quantified secretion machinery elements (SNARE – soluble N-ethylmaleimide sensitive factor attachment protein receptors) complex and SNARE effectors) in hippocampi from electrically kindled animals. In these animals, there is a persistent, asymmetric accumulation of SNARE complexes in the hippocampus ipsilateral to the stimulating electrode, regardless of stimulation site. Treatment with levetiracetam (an antiepileptic drug which specifically binds SV2 (synaptic vesicle protein 2)) dampened this accumulation and delayed kindling. Of the SNARE effectors examined, only SV2, tomosyn, and NSF (N-ethylmaleimide sensitive factor) showed alterations upon kindling. The implications of these findings toward an understanding of epilepsy are discussed.