NMDA receptor-mediated long-term alterations in epileptiform activity in experimental chronic epilepsy

NEUROPHARMACOLOGY

卷:56

Article

Hellier, Jennifer L.¹  White, Andrew²  Williams, Philip A.³  Dudek, F. Edward⁴  Staley, Kevin J.⁵ 

[1] Univ Colorado, Hlth Sci Ctr, Neurosci Program, Boulder, CO 80309 USA

[2] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Boulder, CO 80309 USA

[3] Case Western Reserve Univ, Dept Physiol, Cleveland, OH 44106 USA

[4] Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84108 USA

[5] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA

关键词: Kainate;    Hippocampus;    Depotentiation;    Seizures;   

DOI  :  10.1016/j.neuropharm.2008.09.009

来源: Elsevier

【 摘 要 】

When epileptiform activity is acutely induced in vitro, transient partial blockade of N-methyl-D-aspartic acid (NMDA) receptor-mediated calcium influx leads to selective long-term depotentiation of the synapses involved in the epileptic activity as well as a reduction in the probability of further epileptiform activity. If such selective depotentiation occurred within foci of epileptic activity in vivo, the corresponding long-term reduction in seizure probability could form the basis for a novel treatment of epilepsy. Continuous radiotelemetric EEG monitoring demonstrated modest acute anticonvulsant effects but no long-term reductions in the probability of spontaneous seizures after transient partial blockade of NMDA receptors (NMDAR) during ictal and interictal activity in the kainate animal model of chronic epilepsy. In vitro, depotentiation was induced when NMDAR were partially blocked during epileptiform activity in hippocampal slices from control animals, but not in slices from chronically epileptic rats. However in slices from epileptic animals, depotentiation during epileptiform activity was induced by partial block of NMDAR using NR2B- but not NR2A-selective antagonists. These results suggest that chronic epileptic activity is associated with changes in NMDA receptor-mediated signaling that is reflected in the pharmacology of activity- and NMDA receptor-dependent depotentiation. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free