Partial seizures induced by latrunculin A microperfusion in the mouse hippocampus: Role of extracellular glutamate and NMDA receptors

Abstract

SourceURL:file:///Macintosh%20HD/Users/cruz/Desktop/mol-cell-epi/MOL-CEL.doc We have previously shown that in vivo disruption of F-actin filaments induces acute and chronic seizures in rats and mice. On these basis, we have studied the effect of latrunculin A microperfusion in the mice hippocampus on seizure patterns, actin filaments and NMDA receptors. Latrunculin A (8 mg/ml) was perfused for three consecutive days into the mice hippocampus using microdialysis probes with continuous EEG and video monitoring. After microdialysis experiments, F-actin depolymerization and synaptic and extrasynaptic NR1 protein levels were investigated. Intrahippocampal latrunculin A microdialysis induced partial seizures during the third day of perfusion, and the animals started showing spontaneous partial seizures one month after treatment. Increased levels of extracellular glutamate via microdislysis probes induced seizures in treated mice. F-actin levels were significantly decreased, while NMDA receptor density increased both in synaptic and non-synaptic locations. These results support the hypothesis that actin disruption might be not just a consequence but also a possible cause of epileptic seizures. Actin depolymerization-induced seizures are related to an increase in synaptic and extrasynaptic NMDA receptors and to changes in the extracellular environment. We propose a new experimental model in mice to study the biochemical changes that may lead to chronic seizures, and a method for testing new antiepileptic drugs.